User login
Semaglutide for meaningful weight loss in obesity and diabetes?
A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically meaningful 5% loss in weight for roughly two-thirds of patients with both overweight/obesity and type 2 diabetes, researchers report.
These findings from the Semaglutide Treatment Effect in People With Obesity 2 (STEP 2) trial, one of four phase 3 trials of this drug, which is currently under regulatory review for weight loss, were published March 2 in The Lancet.
More than 1,000 patients (mean initial weight, 100 kg [220 pounds]) were randomly assigned to receive a lifestyle intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they had lost a mean of 9.6%, 7.0%, and 3.4%, respectively, of their starting weight.
In addition, 69% of patients who had received semaglutide 2.4 mg experienced a clinically meaningful 5% loss of weight, compared with 57% of patients who had received the lower dose and 29% of patients who had received placebo.
The higher dose of semaglutide was associated with a greater improvement in cardiometabolic risk factors. The safety profile was similar to that seen with other drugs in this class.
“By far the best results with any weight loss medicine in diabetes”
Importantly, “more than a quarter of participants lost over 15% of their body weight,” senior author Ildiko Lingvay, MD, stressed. This “is by far the best result we had with any weight loss medicine in patients with diabetes,” Dr. Lingvay, of the University of Texas, Dallas, said in a statement from the university.
“The drug works by suppressing appetite centers in the brain to reduce caloric intake,” she explained. “The medication continually tells the body that you just ate, you’re full.”
Similarly, lead author Melanie J. Davies, MD, said that the STEP 2 results “are exciting and represent a new era in weight management in people with type 2 diabetes.
“They mark a real paradigm shift in our ability to treat obesity,” with results closer to those achieved with bariatric surgery, Dr. Davies, of the University of Leicester, England, said in a statement from her institution.
“It is really encouraging,” she continued, “that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure, and blood glucose control.”
Dr. Lingvay noted that on average, patients in the four STEP clinical trials lost 10%-17% of their body weight, “which is a huge step forward compared with all other medications currently available to treat obesity.” She stressed that these results are comparable to the 20%-30% weight loss seen with bariatric surgery.
One of four trials under review
More than 90% of people with type 2 diabetes are overweight or have obesity, and more than 20% of people with obesity have diabetes, wrote Dr. Davies and colleagues.
Semaglutide (Ozempic), administered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is approved by the Food and Drug Administration for the treatment of type 2 diabetes. Dosing studies indicated that it is associated with weight loss.
As previously reported, four trials of the use of semaglutide for weight loss (STEP 1, 2, 3, and 4) have been completed. The combined data were submitted to the FDA on Dec. 4, 2020 (a decision is expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs. placebo were recently published. The STEP 1 trial involved 1,961 adults with obesity or overweight; the STEP 3 trial, 611 adults with obesity or overweight. In each of the trials, some patients also underwent an intensive lifestyle intervention, and some did not. In both trials, patients with type 2 diabetes were excluded.
Topline results from STEP 2 were reported in June 2020.
STEP 2 enrolled patients with type 2 diabetes
STEP 2 involved 1,210 adults in 149 outpatient clinics in 12 countries in Europe, North America, South America, the Middle East, South Africa, and Asia. All participants had type 2 diabetes.
For all patients, the body mass index was ≥27 kg/m2, and the A1c concentration was 7%-10%. The mean BMI was 35.7 kg/m2, and the mean A1c was 8.1%.
The mean age of the patients was 55 years, and 51% were women; 62% were White, 26% were Asian, 13% were Hispanic, 8% were Black, and 4% were of other ethnicity.
Participants were managed with diet and exercise alone or underwent treatment with a stable dose of up to three oral glucose-lowering agents (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for at least 90 days. They were then randomly assigned in 1:1:1 ratio to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.
The starting dose of semaglutide was 0.25 mg/wk; the dose was escalated every 4 weeks to reach the target dose.
All patients received monthly counseling from a dietitian about calories (the goal was a 500-calorie/day deficit) and activity (the goal was 150 minutes of walking or stair climbing per week).
The mean A1c dropped by 1.6% and 1.5% in the semaglutide groups and by 0.4% in the placebo group.
Adverse events were more frequent among the patients who received semaglutide (88% and 82%) than in the placebo group (77%).
Gastrointestinal events that were mainly mild to moderate in severity were reported by 64% of patients in the 2.4-mg semaglutide group, 58% in the 1.0-mg semaglutide group, and 34% in the placebo group.
Semaglutide (Rybelsus) is approved in the United States as a once-daily oral agent for use in type 2 diabetes in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
The study was supported by Novo Nordisk. The authors’ relevant financial relationships are listed in the original article.
A version of this article first appeared on Medscape.com.
A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically meaningful 5% loss in weight for roughly two-thirds of patients with both overweight/obesity and type 2 diabetes, researchers report.
These findings from the Semaglutide Treatment Effect in People With Obesity 2 (STEP 2) trial, one of four phase 3 trials of this drug, which is currently under regulatory review for weight loss, were published March 2 in The Lancet.
More than 1,000 patients (mean initial weight, 100 kg [220 pounds]) were randomly assigned to receive a lifestyle intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they had lost a mean of 9.6%, 7.0%, and 3.4%, respectively, of their starting weight.
In addition, 69% of patients who had received semaglutide 2.4 mg experienced a clinically meaningful 5% loss of weight, compared with 57% of patients who had received the lower dose and 29% of patients who had received placebo.
The higher dose of semaglutide was associated with a greater improvement in cardiometabolic risk factors. The safety profile was similar to that seen with other drugs in this class.
“By far the best results with any weight loss medicine in diabetes”
Importantly, “more than a quarter of participants lost over 15% of their body weight,” senior author Ildiko Lingvay, MD, stressed. This “is by far the best result we had with any weight loss medicine in patients with diabetes,” Dr. Lingvay, of the University of Texas, Dallas, said in a statement from the university.
“The drug works by suppressing appetite centers in the brain to reduce caloric intake,” she explained. “The medication continually tells the body that you just ate, you’re full.”
Similarly, lead author Melanie J. Davies, MD, said that the STEP 2 results “are exciting and represent a new era in weight management in people with type 2 diabetes.
“They mark a real paradigm shift in our ability to treat obesity,” with results closer to those achieved with bariatric surgery, Dr. Davies, of the University of Leicester, England, said in a statement from her institution.
“It is really encouraging,” she continued, “that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure, and blood glucose control.”
Dr. Lingvay noted that on average, patients in the four STEP clinical trials lost 10%-17% of their body weight, “which is a huge step forward compared with all other medications currently available to treat obesity.” She stressed that these results are comparable to the 20%-30% weight loss seen with bariatric surgery.
One of four trials under review
More than 90% of people with type 2 diabetes are overweight or have obesity, and more than 20% of people with obesity have diabetes, wrote Dr. Davies and colleagues.
Semaglutide (Ozempic), administered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is approved by the Food and Drug Administration for the treatment of type 2 diabetes. Dosing studies indicated that it is associated with weight loss.
As previously reported, four trials of the use of semaglutide for weight loss (STEP 1, 2, 3, and 4) have been completed. The combined data were submitted to the FDA on Dec. 4, 2020 (a decision is expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs. placebo were recently published. The STEP 1 trial involved 1,961 adults with obesity or overweight; the STEP 3 trial, 611 adults with obesity or overweight. In each of the trials, some patients also underwent an intensive lifestyle intervention, and some did not. In both trials, patients with type 2 diabetes were excluded.
Topline results from STEP 2 were reported in June 2020.
STEP 2 enrolled patients with type 2 diabetes
STEP 2 involved 1,210 adults in 149 outpatient clinics in 12 countries in Europe, North America, South America, the Middle East, South Africa, and Asia. All participants had type 2 diabetes.
For all patients, the body mass index was ≥27 kg/m2, and the A1c concentration was 7%-10%. The mean BMI was 35.7 kg/m2, and the mean A1c was 8.1%.
The mean age of the patients was 55 years, and 51% were women; 62% were White, 26% were Asian, 13% were Hispanic, 8% were Black, and 4% were of other ethnicity.
Participants were managed with diet and exercise alone or underwent treatment with a stable dose of up to three oral glucose-lowering agents (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for at least 90 days. They were then randomly assigned in 1:1:1 ratio to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.
The starting dose of semaglutide was 0.25 mg/wk; the dose was escalated every 4 weeks to reach the target dose.
All patients received monthly counseling from a dietitian about calories (the goal was a 500-calorie/day deficit) and activity (the goal was 150 minutes of walking or stair climbing per week).
The mean A1c dropped by 1.6% and 1.5% in the semaglutide groups and by 0.4% in the placebo group.
Adverse events were more frequent among the patients who received semaglutide (88% and 82%) than in the placebo group (77%).
Gastrointestinal events that were mainly mild to moderate in severity were reported by 64% of patients in the 2.4-mg semaglutide group, 58% in the 1.0-mg semaglutide group, and 34% in the placebo group.
Semaglutide (Rybelsus) is approved in the United States as a once-daily oral agent for use in type 2 diabetes in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
The study was supported by Novo Nordisk. The authors’ relevant financial relationships are listed in the original article.
A version of this article first appeared on Medscape.com.
A 2.4-mg weekly injection of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide led to a clinically meaningful 5% loss in weight for roughly two-thirds of patients with both overweight/obesity and type 2 diabetes, researchers report.
These findings from the Semaglutide Treatment Effect in People With Obesity 2 (STEP 2) trial, one of four phase 3 trials of this drug, which is currently under regulatory review for weight loss, were published March 2 in The Lancet.
More than 1,000 patients (mean initial weight, 100 kg [220 pounds]) were randomly assigned to receive a lifestyle intervention plus a weekly injection of semaglutide 2.4 mg or semaglutide 1.0 mg or placebo. At 68 weeks, they had lost a mean of 9.6%, 7.0%, and 3.4%, respectively, of their starting weight.
In addition, 69% of patients who had received semaglutide 2.4 mg experienced a clinically meaningful 5% loss of weight, compared with 57% of patients who had received the lower dose and 29% of patients who had received placebo.
The higher dose of semaglutide was associated with a greater improvement in cardiometabolic risk factors. The safety profile was similar to that seen with other drugs in this class.
“By far the best results with any weight loss medicine in diabetes”
Importantly, “more than a quarter of participants lost over 15% of their body weight,” senior author Ildiko Lingvay, MD, stressed. This “is by far the best result we had with any weight loss medicine in patients with diabetes,” Dr. Lingvay, of the University of Texas, Dallas, said in a statement from the university.
“The drug works by suppressing appetite centers in the brain to reduce caloric intake,” she explained. “The medication continually tells the body that you just ate, you’re full.”
Similarly, lead author Melanie J. Davies, MD, said that the STEP 2 results “are exciting and represent a new era in weight management in people with type 2 diabetes.
“They mark a real paradigm shift in our ability to treat obesity,” with results closer to those achieved with bariatric surgery, Dr. Davies, of the University of Leicester, England, said in a statement from her institution.
“It is really encouraging,” she continued, “that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure, and blood glucose control.”
Dr. Lingvay noted that on average, patients in the four STEP clinical trials lost 10%-17% of their body weight, “which is a huge step forward compared with all other medications currently available to treat obesity.” She stressed that these results are comparable to the 20%-30% weight loss seen with bariatric surgery.
One of four trials under review
More than 90% of people with type 2 diabetes are overweight or have obesity, and more than 20% of people with obesity have diabetes, wrote Dr. Davies and colleagues.
Semaglutide (Ozempic), administered subcutaneously at a dose of 0.5 mg to 1 mg weekly, is approved by the Food and Drug Administration for the treatment of type 2 diabetes. Dosing studies indicated that it is associated with weight loss.
As previously reported, four trials of the use of semaglutide for weight loss (STEP 1, 2, 3, and 4) have been completed. The combined data were submitted to the FDA on Dec. 4, 2020 (a decision is expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
The STEP 1 and STEP 3 trials of semaglutide 2.4 mg vs. placebo were recently published. The STEP 1 trial involved 1,961 adults with obesity or overweight; the STEP 3 trial, 611 adults with obesity or overweight. In each of the trials, some patients also underwent an intensive lifestyle intervention, and some did not. In both trials, patients with type 2 diabetes were excluded.
Topline results from STEP 2 were reported in June 2020.
STEP 2 enrolled patients with type 2 diabetes
STEP 2 involved 1,210 adults in 149 outpatient clinics in 12 countries in Europe, North America, South America, the Middle East, South Africa, and Asia. All participants had type 2 diabetes.
For all patients, the body mass index was ≥27 kg/m2, and the A1c concentration was 7%-10%. The mean BMI was 35.7 kg/m2, and the mean A1c was 8.1%.
The mean age of the patients was 55 years, and 51% were women; 62% were White, 26% were Asian, 13% were Hispanic, 8% were Black, and 4% were of other ethnicity.
Participants were managed with diet and exercise alone or underwent treatment with a stable dose of up to three oral glucose-lowering agents (metformin, sulfonylureas, SGLT2 inhibitors, or thiazolidinediones) for at least 90 days. They were then randomly assigned in 1:1:1 ratio to receive semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo.
The starting dose of semaglutide was 0.25 mg/wk; the dose was escalated every 4 weeks to reach the target dose.
All patients received monthly counseling from a dietitian about calories (the goal was a 500-calorie/day deficit) and activity (the goal was 150 minutes of walking or stair climbing per week).
The mean A1c dropped by 1.6% and 1.5% in the semaglutide groups and by 0.4% in the placebo group.
Adverse events were more frequent among the patients who received semaglutide (88% and 82%) than in the placebo group (77%).
Gastrointestinal events that were mainly mild to moderate in severity were reported by 64% of patients in the 2.4-mg semaglutide group, 58% in the 1.0-mg semaglutide group, and 34% in the placebo group.
Semaglutide (Rybelsus) is approved in the United States as a once-daily oral agent for use in type 2 diabetes in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
The study was supported by Novo Nordisk. The authors’ relevant financial relationships are listed in the original article.
A version of this article first appeared on Medscape.com.
Semaglutide for weight loss? A good first STEP, with caveats
The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.
“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.
The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.
“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.
However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”
Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.
“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.
However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”
Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.
Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.
And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.
In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
‘Pressing need’ to address obesity; semaglutide filed for obesity
There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.
Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.
In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”
Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.
Topline results from STEP 1 were presented June 4, 2020.
And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.
The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
Most patients had 5% weight loss with semaglutide
The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m2 or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.
Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).
On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.
Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.
Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).
Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).
At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).
Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).
About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.
Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.
In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
GI disorders and ‘important limitations’
More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).
More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.
Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.
Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.
The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.
A version of this article first appeared on Medscape.com.
The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.
“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.
The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.
“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.
However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”
Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.
“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.
However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”
Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.
Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.
And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.
In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
‘Pressing need’ to address obesity; semaglutide filed for obesity
There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.
Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.
In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”
Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.
Topline results from STEP 1 were presented June 4, 2020.
And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.
The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
Most patients had 5% weight loss with semaglutide
The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m2 or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.
Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).
On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.
Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.
Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).
Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).
At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).
Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).
About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.
Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.
In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
GI disorders and ‘important limitations’
More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).
More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.
Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.
Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.
The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.
A version of this article first appeared on Medscape.com.
The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.
“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.
The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.
“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.
However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”
Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.
“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.
However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”
Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.
Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.
And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.
In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
‘Pressing need’ to address obesity; semaglutide filed for obesity
There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.
Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.
In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”
Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.
Topline results from STEP 1 were presented June 4, 2020.
And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.
The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
Most patients had 5% weight loss with semaglutide
The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m2 or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.
Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).
On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.
Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.
Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).
Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).
At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).
Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).
About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.
Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.
In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
GI disorders and ‘important limitations’
More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).
More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.
Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.
Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.
The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.
A version of this article first appeared on Medscape.com.
Bariatric surgery gives 10-year cure for some advanced diabetes
A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.
That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.
Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.
These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.
“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.
Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.
Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.
“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
“Reassuring results, will make a difference in the field”
“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.
There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.
“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.
And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.
Diabetes for at least 5 years, mid 40s, half on insulin
Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.
Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.
The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.
Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.
Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.
At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.
At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
First 2 years after surgery is key
“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”
Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.
The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
Better risk-to-benefit ratio with Roux-en-y gastric bypass
No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.
Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.
This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.
The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.
A version of this article first appeared on Medscape.com.
A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.
That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.
Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.
These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.
“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.
Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.
Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.
“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
“Reassuring results, will make a difference in the field”
“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.
There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.
“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.
And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.
Diabetes for at least 5 years, mid 40s, half on insulin
Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.
Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.
The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.
Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.
Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.
At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.
At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
First 2 years after surgery is key
“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”
Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.
The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
Better risk-to-benefit ratio with Roux-en-y gastric bypass
No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.
Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.
This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.
The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.
A version of this article first appeared on Medscape.com.
A small, single-center randomized trial of patients with obesity and advanced type 2 diabetes, defined as diabetes for ≥ 5 years and A1c ≥ 7%, found that a quarter to a half of patients who had metabolic surgery had diabetes remission (cure) that lasted 5-9 years.
That is, of the 60 randomized patients, 50% who had biliopancreatic diversion and 25% who had Roux-en-Y gastric bypass – but none who had received current medical therapy – still had diabetes remission a decade later.
Until now, there had only been 5-year follow-up data from this and similar trials, Geltrude Mingrone, MD, PhD, and colleagues noted in the study published online Jan. 23 in The Lancet.
These results provide “the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive, and irreversible,” senior author Francesco Rubino, MD, chair of bariatric and metabolic surgery at King’s College London, said in a statement from his institution.
“The results of this trial will make a noticeable difference in the field and convince even the most skeptical of clinicians about the role of metabolic surgery as part of optimal care for their patients with difficult to control type 2 diabetes,” predicted two editorialists.
Alexander D. Miras, PhD, section of metabolism, digestion, and reproduction, Imperial College London, and Carel le Roux, MBChB, PhD, of the Diabetes Complications Research Centre, University College Dublin, penned the accompanying commentary.
Patients who had metabolic surgery also had greater weight loss, reduced medication use, lower cardiovascular risk, better quality of life, and a lower incidence of diabetes-related complications compared with those who received medical therapy.
“Clinicians and policymakers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes,” advised Dr. Mingrone of King’s College London and the Catholic University of Rome, and colleagues.
“Reassuring results, will make a difference in the field”
“It is reassuring that we now have 10-year data showing greater efficacy of metabolic surgery than conventional medical therapy,” Dr. Miras and Dr. le Roux wrote in their commentary.
There were no unexpected risks associated with surgery, they noted, and the findings are consistent with those of 12 other randomized controlled trials in the past 12 years.
“New generations of diabetologists are now more open to the use of metabolic surgery for patients with suboptimal responses to medical treatments,” they wrote, rather than endlessly intensifying insulin and blaming poor response on poor compliance.
And Dr. Miras and Dr. le Roux “eagerly await” 10-year data from the 150-patient STAMPEDE trial – which is examining sleeve gastrectomy, currently the most widely performed bariatric procedure, as well as Roux-en-Y gastric bypass and medical therapy – following the 5-year results published in 2017.
Diabetes for at least 5 years, mid 40s, half on insulin
Dr. Mingrone and colleagues previously reported 5-year findings from the 60 patients with obesity and advanced diabetes who were seen in a single center in Rome and randomized to three treatments (20 in each group) in 2009-2011.
Biliopancreatic diversion “remains infrequently performed but is still considered the best operation for glycemic control,” the researchers noted.
The primary endpoint was diabetes remission at 2 years (fasting plasma glucose < 100 mg/dL [5.6 mmol/L] and A1c < 6.5%) without the need for ongoing pharmacological treatment for at least 1 year.
Patients were a mean age of 44 years and had a mean body mass index of 44 kg/m2. About half were men. They had diabetes for a mean of 5.8 years and an average A1c of 8.6%. About half were taking insulin.
Patient retention rate was high (95%) and trial outcomes were assessed by nonsurgeons.
At 10 years, patients’ mean A1c had dropped to 6.4%, 6.7%, and 7.6%, in the biliopancreatic diversion, Roux-en-Y gastric bypass, and medical therapy groups, respectively; only 2.5% of patients in the surgery groups, versus 53% in the medical therapy group, required insulin.
At study end, patients in the surgery groups had lost about 29% of their initial weight versus a weight loss of 4.2% in the medical therapy group.
First 2 years after surgery is key
“We also learnt that patients who do not go into remission after 2 years are very unlikely to ever do so,” Dr. Miras and Dr. le Roux observed, which “might help us to intensify modern and potent glucose-lowering therapies like SGLT2 inhibitors and GLP-1 receptor agonists earlier after metabolic surgery.”
Ten of 19 patients (53%) in the biliopancreatic diversion group and 10 of 15 patients (67%) in the Roux-en-Y gastric bypass group who had diabetes remission at 2 years had a diabetes relapse, but at 10 years, they all had adequate glycemic control (mean A1c 6.7%), despite drastically reduced use of diabetes medications.
The two patients who crossed over to surgery from the medical therapy group had postoperative diabetes remission, which was maintained at 10 years in one patient.
Better risk-to-benefit ratio with Roux-en-y gastric bypass
No patient in the medical therapy group had a serious adverse event, but one patient in each surgery group had deep vein thrombosis or pulmonary embolism, and one patient in the biliopancreatic diversion group had an episode of atrial fibrillation. There were no late surgical complications.
Iron deficiency and mild osteopenia occurred in both surgical groups, but were more common in the biliopancreatic diversion group. And osteoporosis, transient nyctalopia (night blindness) due to vitamin A deficiency, and kidney stones were observed only with biliopancreatic diversion.
This suggests that despite the greater antidiabetic potential of biliopancreatic diversion, Roux-en-Y gastric bypass might have a more favorable risk-to-benefit profile as a standard surgical option for the treatment of type 2 diabetes, Dr. Mingrone and colleagues concluded.
The authors and Dr. Miras have reported no relevant financial relationships. Dr. le Roux has reported receiving funding from the Science Foundation Ireland, the Health Research Board, and the Irish Research Council for type 2 diabetes research, and serves on several advisory boards outside of the scope of the current study.
A version of this article first appeared on Medscape.com.
Monoclonal antibody drops fat, ups muscle in obesity, diabetes
In a phase 2 randomized clinical trial of adults with type 2 diabetes and obesity, investigational drug bimagrumab (BYM338, Novartis) – a monoclonal antibody that blocks activin type II receptors and stimulates skeletal muscle growth – led to big reductions in total body fat mass and A1c and significant increases in lean mass compared with placebo.
The efficacy and safety findings “suggest that blockade of the activin receptor with bimagrumab could provide a novel pharmacologic approach for managing patients with type 2 diabetes with excess adiposity,” Steven B. Heymsfield, MD, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, and colleagues reported in their study, published online Jan. 13 in JAMA Network Open.
Preliminary findings from the study of 75 patients treated for 48 weeks – in which neither group ate less despite intensive nutrition advice – were presented at Obesity Week in 2019.
As reported then, Lee M. Kaplan, MD, PhD, noted that the 6.5% weight loss in the bimagrumab group was similar to that seen with antiobesity medications that suppress appetite.
“What it suggests,” he said in an interview, “is that there may be a completely new mechanism at play here,” because patients receiving bimagrumab weren’t eating less but were losing the same amount of weight as reported for weight-loss drugs that work by decreasing appetite.
“Is this going to be the kind of complementary drug with a different mechanism that’s going to augment the effects of other drugs?” wondered Dr. Kaplan, director of the Obesity, Metabolism & Nutrition Institute at Massachusetts General Hospital, Boston, who has previously served as a scientific consultant to Novartis.
Asked about future plans for bimagrumab, a Novartis spokesperson said in an interview, “We are currently reviewing the program strategy and considering next steps.”
Four FDA-approved weight-loss drugs now approved
The Food and Drug Administration approval for lorcaserin (Belviq, Belviq XR, Eisai) for weight loss was rescinded on Feb. 13, 2020, when a postmarketing trial revealed an increased occurrence of cancer, leaving four drugs approved for weight loss in the United States, plus several drugs in development, Dr. Heymsfield and colleagues wrote.
The current phase 2 trial was designed to determine the safety and efficacy of bimagrumab – which had originally been studied to see if it would increase lean muscle mass in people with sarcopenia – on total body fat mass and glycemic control in patients with type 2 diabetes and overweight or obesity.
Researchers enrolled 75 adults at eight sites in the United States and one in Wales, United Kingdom, from 2017 to 2019.
On average, patients were 60 years old with an A1c of 7.8% and a body mass index of 32.9 kg/m2; they weighed 93.6 kg and had a fat mass of 35 kg.
Patients received an intravenous infusion of bimagrumab (10 mg/kg up to 1,200 mg in 5% dextrose solution) or placebo (5% dextrose solution) every 4 weeks for 48 weeks. They met with a registered dietitian at each monthly study visit and had a virtual check-in between visits.
Participants were advised to follow a diet that would cut 500 calories a day and encouraged to follow the American Diabetes Association walking program.
Body fat mass was measured by dual-energy x-ray absorptiometry (DEXA).
There were more women in the bimagrumab group than in the placebo group (62% vs. 32%), but baseline BMI, total body fat mass, and A1c were similar in both groups.
Same caloric intake, less fat tissue, more muscle, smaller waist
At 48 weeks in the bimagrumab vs. placebo group, there was on average (all P < .001):
- A loss of 20.5% vs. 0.5% (−7.5 vs. −0.2 kg) of total body fat mass.
- A loss of 6.5% vs. 0.8% (−5.9 vs. −0.8 kg) of body weight.
- A gain of 3.6% vs. a loss of 0.8% (1.7 vs. −0.4 kg) of lean mass.
Similarly, the relatively large between-group differences in total body fat mass and body weight at 48 weeks with bimagrumab were accompanied by favorable differences in BMI (−2.19 vs. −0.28 kg/m2; P < .001) and waist circumference (−9.0 vs. 0.5 cm; P < .001), the investigators pointed out.
Moreover, the reduction of abdominal visceral adipose tissue and waist circumference with bimagrumab “was nearly twice that observed in a recently published study of patients with type 2 diabetes treated with an intensive lifestyle program and the glucagon-like peptide 1 (GLP-1) agonist liraglutide,” they noted.
This highlights “the importance of moving away from body weight as a primary efficacy marker of drugs to more metabolically relevant endpoints.”
Also, A1c decreased by 0.76% in the bimagrumab group and increased by 0.04% in the placebo group (P = .005).
Serious adverse events occurred in three patients (8%) in the bimagrumab group (elevated lipase, epigastric pain, pancreatitis, pneumonia) and three patients (8%) in the placebo group (cellulitis, acute coronary syndrome, acute myocardial infarction, worsening gastroparesis, thermal burn).
Adverse events were reported by 31 of 37 patients in the bimagrumab group, most often mild diarrhea (41%) and muscle spasms (41%), and 31 of 38 patients in the placebo group, most often headache (13%) and upper respiratory tract infection (13%).
The study was funded by Novartis. Dr. Heymsfield has reported receiving personal fees from Tanita and Medifast outside the submitted work. Disclosures for the other authors are listed in the article. Dr. Kaplan has reported previously serving as a scientific consultant to Novartis.
A version of this article first appeared on Medscape.com.
In a phase 2 randomized clinical trial of adults with type 2 diabetes and obesity, investigational drug bimagrumab (BYM338, Novartis) – a monoclonal antibody that blocks activin type II receptors and stimulates skeletal muscle growth – led to big reductions in total body fat mass and A1c and significant increases in lean mass compared with placebo.
The efficacy and safety findings “suggest that blockade of the activin receptor with bimagrumab could provide a novel pharmacologic approach for managing patients with type 2 diabetes with excess adiposity,” Steven B. Heymsfield, MD, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, and colleagues reported in their study, published online Jan. 13 in JAMA Network Open.
Preliminary findings from the study of 75 patients treated for 48 weeks – in which neither group ate less despite intensive nutrition advice – were presented at Obesity Week in 2019.
As reported then, Lee M. Kaplan, MD, PhD, noted that the 6.5% weight loss in the bimagrumab group was similar to that seen with antiobesity medications that suppress appetite.
“What it suggests,” he said in an interview, “is that there may be a completely new mechanism at play here,” because patients receiving bimagrumab weren’t eating less but were losing the same amount of weight as reported for weight-loss drugs that work by decreasing appetite.
“Is this going to be the kind of complementary drug with a different mechanism that’s going to augment the effects of other drugs?” wondered Dr. Kaplan, director of the Obesity, Metabolism & Nutrition Institute at Massachusetts General Hospital, Boston, who has previously served as a scientific consultant to Novartis.
Asked about future plans for bimagrumab, a Novartis spokesperson said in an interview, “We are currently reviewing the program strategy and considering next steps.”
Four FDA-approved weight-loss drugs now approved
The Food and Drug Administration approval for lorcaserin (Belviq, Belviq XR, Eisai) for weight loss was rescinded on Feb. 13, 2020, when a postmarketing trial revealed an increased occurrence of cancer, leaving four drugs approved for weight loss in the United States, plus several drugs in development, Dr. Heymsfield and colleagues wrote.
The current phase 2 trial was designed to determine the safety and efficacy of bimagrumab – which had originally been studied to see if it would increase lean muscle mass in people with sarcopenia – on total body fat mass and glycemic control in patients with type 2 diabetes and overweight or obesity.
Researchers enrolled 75 adults at eight sites in the United States and one in Wales, United Kingdom, from 2017 to 2019.
On average, patients were 60 years old with an A1c of 7.8% and a body mass index of 32.9 kg/m2; they weighed 93.6 kg and had a fat mass of 35 kg.
Patients received an intravenous infusion of bimagrumab (10 mg/kg up to 1,200 mg in 5% dextrose solution) or placebo (5% dextrose solution) every 4 weeks for 48 weeks. They met with a registered dietitian at each monthly study visit and had a virtual check-in between visits.
Participants were advised to follow a diet that would cut 500 calories a day and encouraged to follow the American Diabetes Association walking program.
Body fat mass was measured by dual-energy x-ray absorptiometry (DEXA).
There were more women in the bimagrumab group than in the placebo group (62% vs. 32%), but baseline BMI, total body fat mass, and A1c were similar in both groups.
Same caloric intake, less fat tissue, more muscle, smaller waist
At 48 weeks in the bimagrumab vs. placebo group, there was on average (all P < .001):
- A loss of 20.5% vs. 0.5% (−7.5 vs. −0.2 kg) of total body fat mass.
- A loss of 6.5% vs. 0.8% (−5.9 vs. −0.8 kg) of body weight.
- A gain of 3.6% vs. a loss of 0.8% (1.7 vs. −0.4 kg) of lean mass.
Similarly, the relatively large between-group differences in total body fat mass and body weight at 48 weeks with bimagrumab were accompanied by favorable differences in BMI (−2.19 vs. −0.28 kg/m2; P < .001) and waist circumference (−9.0 vs. 0.5 cm; P < .001), the investigators pointed out.
Moreover, the reduction of abdominal visceral adipose tissue and waist circumference with bimagrumab “was nearly twice that observed in a recently published study of patients with type 2 diabetes treated with an intensive lifestyle program and the glucagon-like peptide 1 (GLP-1) agonist liraglutide,” they noted.
This highlights “the importance of moving away from body weight as a primary efficacy marker of drugs to more metabolically relevant endpoints.”
Also, A1c decreased by 0.76% in the bimagrumab group and increased by 0.04% in the placebo group (P = .005).
Serious adverse events occurred in three patients (8%) in the bimagrumab group (elevated lipase, epigastric pain, pancreatitis, pneumonia) and three patients (8%) in the placebo group (cellulitis, acute coronary syndrome, acute myocardial infarction, worsening gastroparesis, thermal burn).
Adverse events were reported by 31 of 37 patients in the bimagrumab group, most often mild diarrhea (41%) and muscle spasms (41%), and 31 of 38 patients in the placebo group, most often headache (13%) and upper respiratory tract infection (13%).
The study was funded by Novartis. Dr. Heymsfield has reported receiving personal fees from Tanita and Medifast outside the submitted work. Disclosures for the other authors are listed in the article. Dr. Kaplan has reported previously serving as a scientific consultant to Novartis.
A version of this article first appeared on Medscape.com.
In a phase 2 randomized clinical trial of adults with type 2 diabetes and obesity, investigational drug bimagrumab (BYM338, Novartis) – a monoclonal antibody that blocks activin type II receptors and stimulates skeletal muscle growth – led to big reductions in total body fat mass and A1c and significant increases in lean mass compared with placebo.
The efficacy and safety findings “suggest that blockade of the activin receptor with bimagrumab could provide a novel pharmacologic approach for managing patients with type 2 diabetes with excess adiposity,” Steven B. Heymsfield, MD, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, and colleagues reported in their study, published online Jan. 13 in JAMA Network Open.
Preliminary findings from the study of 75 patients treated for 48 weeks – in which neither group ate less despite intensive nutrition advice – were presented at Obesity Week in 2019.
As reported then, Lee M. Kaplan, MD, PhD, noted that the 6.5% weight loss in the bimagrumab group was similar to that seen with antiobesity medications that suppress appetite.
“What it suggests,” he said in an interview, “is that there may be a completely new mechanism at play here,” because patients receiving bimagrumab weren’t eating less but were losing the same amount of weight as reported for weight-loss drugs that work by decreasing appetite.
“Is this going to be the kind of complementary drug with a different mechanism that’s going to augment the effects of other drugs?” wondered Dr. Kaplan, director of the Obesity, Metabolism & Nutrition Institute at Massachusetts General Hospital, Boston, who has previously served as a scientific consultant to Novartis.
Asked about future plans for bimagrumab, a Novartis spokesperson said in an interview, “We are currently reviewing the program strategy and considering next steps.”
Four FDA-approved weight-loss drugs now approved
The Food and Drug Administration approval for lorcaserin (Belviq, Belviq XR, Eisai) for weight loss was rescinded on Feb. 13, 2020, when a postmarketing trial revealed an increased occurrence of cancer, leaving four drugs approved for weight loss in the United States, plus several drugs in development, Dr. Heymsfield and colleagues wrote.
The current phase 2 trial was designed to determine the safety and efficacy of bimagrumab – which had originally been studied to see if it would increase lean muscle mass in people with sarcopenia – on total body fat mass and glycemic control in patients with type 2 diabetes and overweight or obesity.
Researchers enrolled 75 adults at eight sites in the United States and one in Wales, United Kingdom, from 2017 to 2019.
On average, patients were 60 years old with an A1c of 7.8% and a body mass index of 32.9 kg/m2; they weighed 93.6 kg and had a fat mass of 35 kg.
Patients received an intravenous infusion of bimagrumab (10 mg/kg up to 1,200 mg in 5% dextrose solution) or placebo (5% dextrose solution) every 4 weeks for 48 weeks. They met with a registered dietitian at each monthly study visit and had a virtual check-in between visits.
Participants were advised to follow a diet that would cut 500 calories a day and encouraged to follow the American Diabetes Association walking program.
Body fat mass was measured by dual-energy x-ray absorptiometry (DEXA).
There were more women in the bimagrumab group than in the placebo group (62% vs. 32%), but baseline BMI, total body fat mass, and A1c were similar in both groups.
Same caloric intake, less fat tissue, more muscle, smaller waist
At 48 weeks in the bimagrumab vs. placebo group, there was on average (all P < .001):
- A loss of 20.5% vs. 0.5% (−7.5 vs. −0.2 kg) of total body fat mass.
- A loss of 6.5% vs. 0.8% (−5.9 vs. −0.8 kg) of body weight.
- A gain of 3.6% vs. a loss of 0.8% (1.7 vs. −0.4 kg) of lean mass.
Similarly, the relatively large between-group differences in total body fat mass and body weight at 48 weeks with bimagrumab were accompanied by favorable differences in BMI (−2.19 vs. −0.28 kg/m2; P < .001) and waist circumference (−9.0 vs. 0.5 cm; P < .001), the investigators pointed out.
Moreover, the reduction of abdominal visceral adipose tissue and waist circumference with bimagrumab “was nearly twice that observed in a recently published study of patients with type 2 diabetes treated with an intensive lifestyle program and the glucagon-like peptide 1 (GLP-1) agonist liraglutide,” they noted.
This highlights “the importance of moving away from body weight as a primary efficacy marker of drugs to more metabolically relevant endpoints.”
Also, A1c decreased by 0.76% in the bimagrumab group and increased by 0.04% in the placebo group (P = .005).
Serious adverse events occurred in three patients (8%) in the bimagrumab group (elevated lipase, epigastric pain, pancreatitis, pneumonia) and three patients (8%) in the placebo group (cellulitis, acute coronary syndrome, acute myocardial infarction, worsening gastroparesis, thermal burn).
Adverse events were reported by 31 of 37 patients in the bimagrumab group, most often mild diarrhea (41%) and muscle spasms (41%), and 31 of 38 patients in the placebo group, most often headache (13%) and upper respiratory tract infection (13%).
The study was funded by Novartis. Dr. Heymsfield has reported receiving personal fees from Tanita and Medifast outside the submitted work. Disclosures for the other authors are listed in the article. Dr. Kaplan has reported previously serving as a scientific consultant to Novartis.
A version of this article first appeared on Medscape.com.
Marijuana use tied to repeat MI, stroke after percutaneous coronary intervention
in separate studies.
Rhushik Bhuva, MD, presented the recurrent-MI results from a national U.S. study, and Sang Gune K. Yoo, MD, presented the PCI study, which used data from a Michigan cohort. The studies were presented at the American Heart Association scientific sessions.
Both studies “add to our accumulating knowledge of the cardiovascular risks of marijuana,” Ersilia M. DeFilippis, MD, a cardiology fellow at Columbia University Irvine Medical Center, New York, who was not involved with this research, said in an interview.
Dr. DeFilippis and the two study authors say clinicians and patients need to be more aware of cardiovascular risks from smoking marijuana, and they call for more patient screening, counseling, and research.
Need for screening and counseling
Marijuana is a Schedule 1 controlled substance in the United States, which makes it illegal to conduct rigorous controlled trials of marijuana products. Existing knowledge is therefore based on observational studies, Dr. DeFilippis noted.
She was lead author of a review of marijuana use by patients with cardiovascular disease. The review was published in the Journal of the American College of Cardiology. An AHA scientific statement about marijuana and cardiovascular health was published in Circulation.
Both documents drew attention to risks from marijuana use in patients with cardiovascular disease.
Until more data are available, “I think it is absolutely critical” that cardiologists and general providers screen patients for marijuana use, “either at the time of their MI or ideally prior to that, when they are making a cardiovascular risk assessment,” said Dr. DeFilippis.
That is also the time to “counsel patients, especially those who have had an MI, about risks associated with continuing to use marijuana.”
Importantly, providers and patients need to be aware that “cannabinoids, through the cytochrome P450 system, can interact with well-known cardiovascular medications, which we know provide benefit in the post-MI period,” she added. “For example, marijuana can interfere with beta-blockers, statins, antiarrhythmics, and certain anticoagulants.”
Dr. Bhuva, a cardiology fellow with the Wright Center for Community Health, Scranton, Pa., said that it is “concerning” that “recurrent heart attacks and cardiac interventions [were] higher among cannabis users, even though they were younger and had fewer risk factors for heart disease.
“Spreading awareness regarding the potential risk of recurrent heart attacks in middle-aged, African American, and male cannabis users and screening them at an earlier age for potential risk factors of future heart attacks should be encouraged among clinicians,” he urged in a statement from the AHA.
Dr. Yoo, an internal medicine resident at the University of Michigan, Ann Arbor, pointed out that, in their study of patients who underwent PCI after MI or because they had coronary artery disease, those who smoked or vaped marijuana were younger and were more likely to be male. They were less likely to have traditional cardiovascular risk factors except for smoking tobacco, which was highly prevalent.
After propensity matching, patients who used marijuana had a 1.5-fold increased risk of in-hospital bleeding and an 11-fold higher risk for in-hospital stroke following PCI.
However, the absolute number of strokes in PCI was small, and the confidence interval was wide (indicating a large uncertainty), Dr. Yoo said in an interview.
These risks “should not deter patients from undergoing these [lifesaving] procedures,” he said; however, clinicians should be aware of these risks with marijuana use and should screen and counsel patients about this.
Hospitalized patients with prior MI
Dr. Bhuva and colleagues identified patients from the National Inpatient Sample who were hospitalized in the United States from 2007 to 2014 and who had experienced a prior MI and had undergone revascularization with PCI or coronary artery bypass grafting (CABG).
There were about 8 million hospital stays per year. The database did not specify the type of marijuana that patients used.
During the 8-year study period, many states legalized or decriminalized medical and/or recreational marijuana, and marijuana use increased steadily, from 0.2% to 0.7%.
Compared with nonusers, those who used marijuana were younger (median age, 53 vs. 72 years), and there were more men (77% vs. 62%) or Black persons (34% vs. 10%) (all P < .001). Fewer marijuana users had hypertension (72% vs. 75%), diabetes (24% vs. 33%), or dyslipidemia (51% vs. 58%) (all P < .001). More marijuana users underwent a repeat MI (67% vs. 41%).
On the other hand, marijuana users, who were younger and healthier than the other patients, were less likely to die during hospitalization for a recurrent MI (0.8% vs. 2.5%), and their hospital costs were lower.
The researchers acknowledged that study limitations include lack of information about marijuana type (smoked, edible, medicinal, or recreational) or dose, as well as the time from marijuana use to cardiac event.
In-Hospital outcomes after PCI
Dr. Yoo and colleagues analyzed data from patients who underwent PCI from Jan. 1, 2013, to Oct. 1, 2016, at Michigan’s 48 nonfederal hospitals, which are part of the Blue Cross Blue Shield Michigan Cardiovascular Consortium PCI registry.
In this cohort, 3,970 patients (3.5%) had smoked or vaped marijuana in the month prior to PCI, and 109,507 patients had not done so. The marijuana users were younger (mean age, 54 vs. 66 years) and were more likely to be male (79% vs. 67%) and to smoke cigarettes (73% vs. 27%).
They were less likely to have hypertension, type 2 diabetes, dyslipidemia, cerebrovascular disease, or prior CABG and were equally likely to have had a prior MI (36%).
Compared with nonusers, marijuana users were more likely to present with non–ST-elevation MI (30% vs. 23%) or ST-elevation MI (27% vs. 16%) and were less likely to present with angina.
Using propensity score matching, the researchers matched 3,803 marijuana users with the same number of nonusers.
In the matched cohort, patients who used marijuana had a greater risk of in-hospital bleeding (adjusted odds ratio, 1.54; 95% confidence interval, 1.20-1.97; P < .001) or stroke (aOR, 11.01; 95% CI, 1.32-91.67; P = .026) following PCI.
Marijuana users had a lower risk for acute kidney injury (2.2% vs. 2.9%; P = .007). Transfusion and mortality rates were similar in both groups.
The researchers acknowledged study limitations, including the fact that it did not include marijuana edibles, that the results may not be generalizable, and that marijuana use is now likely more common in Michigan following legalization of recreational marijuana in 2018.
Dr. Bhuva, Dr. Yoo, and Dr. DeFilippis have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
in separate studies.
Rhushik Bhuva, MD, presented the recurrent-MI results from a national U.S. study, and Sang Gune K. Yoo, MD, presented the PCI study, which used data from a Michigan cohort. The studies were presented at the American Heart Association scientific sessions.
Both studies “add to our accumulating knowledge of the cardiovascular risks of marijuana,” Ersilia M. DeFilippis, MD, a cardiology fellow at Columbia University Irvine Medical Center, New York, who was not involved with this research, said in an interview.
Dr. DeFilippis and the two study authors say clinicians and patients need to be more aware of cardiovascular risks from smoking marijuana, and they call for more patient screening, counseling, and research.
Need for screening and counseling
Marijuana is a Schedule 1 controlled substance in the United States, which makes it illegal to conduct rigorous controlled trials of marijuana products. Existing knowledge is therefore based on observational studies, Dr. DeFilippis noted.
She was lead author of a review of marijuana use by patients with cardiovascular disease. The review was published in the Journal of the American College of Cardiology. An AHA scientific statement about marijuana and cardiovascular health was published in Circulation.
Both documents drew attention to risks from marijuana use in patients with cardiovascular disease.
Until more data are available, “I think it is absolutely critical” that cardiologists and general providers screen patients for marijuana use, “either at the time of their MI or ideally prior to that, when they are making a cardiovascular risk assessment,” said Dr. DeFilippis.
That is also the time to “counsel patients, especially those who have had an MI, about risks associated with continuing to use marijuana.”
Importantly, providers and patients need to be aware that “cannabinoids, through the cytochrome P450 system, can interact with well-known cardiovascular medications, which we know provide benefit in the post-MI period,” she added. “For example, marijuana can interfere with beta-blockers, statins, antiarrhythmics, and certain anticoagulants.”
Dr. Bhuva, a cardiology fellow with the Wright Center for Community Health, Scranton, Pa., said that it is “concerning” that “recurrent heart attacks and cardiac interventions [were] higher among cannabis users, even though they were younger and had fewer risk factors for heart disease.
“Spreading awareness regarding the potential risk of recurrent heart attacks in middle-aged, African American, and male cannabis users and screening them at an earlier age for potential risk factors of future heart attacks should be encouraged among clinicians,” he urged in a statement from the AHA.
Dr. Yoo, an internal medicine resident at the University of Michigan, Ann Arbor, pointed out that, in their study of patients who underwent PCI after MI or because they had coronary artery disease, those who smoked or vaped marijuana were younger and were more likely to be male. They were less likely to have traditional cardiovascular risk factors except for smoking tobacco, which was highly prevalent.
After propensity matching, patients who used marijuana had a 1.5-fold increased risk of in-hospital bleeding and an 11-fold higher risk for in-hospital stroke following PCI.
However, the absolute number of strokes in PCI was small, and the confidence interval was wide (indicating a large uncertainty), Dr. Yoo said in an interview.
These risks “should not deter patients from undergoing these [lifesaving] procedures,” he said; however, clinicians should be aware of these risks with marijuana use and should screen and counsel patients about this.
Hospitalized patients with prior MI
Dr. Bhuva and colleagues identified patients from the National Inpatient Sample who were hospitalized in the United States from 2007 to 2014 and who had experienced a prior MI and had undergone revascularization with PCI or coronary artery bypass grafting (CABG).
There were about 8 million hospital stays per year. The database did not specify the type of marijuana that patients used.
During the 8-year study period, many states legalized or decriminalized medical and/or recreational marijuana, and marijuana use increased steadily, from 0.2% to 0.7%.
Compared with nonusers, those who used marijuana were younger (median age, 53 vs. 72 years), and there were more men (77% vs. 62%) or Black persons (34% vs. 10%) (all P < .001). Fewer marijuana users had hypertension (72% vs. 75%), diabetes (24% vs. 33%), or dyslipidemia (51% vs. 58%) (all P < .001). More marijuana users underwent a repeat MI (67% vs. 41%).
On the other hand, marijuana users, who were younger and healthier than the other patients, were less likely to die during hospitalization for a recurrent MI (0.8% vs. 2.5%), and their hospital costs were lower.
The researchers acknowledged that study limitations include lack of information about marijuana type (smoked, edible, medicinal, or recreational) or dose, as well as the time from marijuana use to cardiac event.
In-Hospital outcomes after PCI
Dr. Yoo and colleagues analyzed data from patients who underwent PCI from Jan. 1, 2013, to Oct. 1, 2016, at Michigan’s 48 nonfederal hospitals, which are part of the Blue Cross Blue Shield Michigan Cardiovascular Consortium PCI registry.
In this cohort, 3,970 patients (3.5%) had smoked or vaped marijuana in the month prior to PCI, and 109,507 patients had not done so. The marijuana users were younger (mean age, 54 vs. 66 years) and were more likely to be male (79% vs. 67%) and to smoke cigarettes (73% vs. 27%).
They were less likely to have hypertension, type 2 diabetes, dyslipidemia, cerebrovascular disease, or prior CABG and were equally likely to have had a prior MI (36%).
Compared with nonusers, marijuana users were more likely to present with non–ST-elevation MI (30% vs. 23%) or ST-elevation MI (27% vs. 16%) and were less likely to present with angina.
Using propensity score matching, the researchers matched 3,803 marijuana users with the same number of nonusers.
In the matched cohort, patients who used marijuana had a greater risk of in-hospital bleeding (adjusted odds ratio, 1.54; 95% confidence interval, 1.20-1.97; P < .001) or stroke (aOR, 11.01; 95% CI, 1.32-91.67; P = .026) following PCI.
Marijuana users had a lower risk for acute kidney injury (2.2% vs. 2.9%; P = .007). Transfusion and mortality rates were similar in both groups.
The researchers acknowledged study limitations, including the fact that it did not include marijuana edibles, that the results may not be generalizable, and that marijuana use is now likely more common in Michigan following legalization of recreational marijuana in 2018.
Dr. Bhuva, Dr. Yoo, and Dr. DeFilippis have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
in separate studies.
Rhushik Bhuva, MD, presented the recurrent-MI results from a national U.S. study, and Sang Gune K. Yoo, MD, presented the PCI study, which used data from a Michigan cohort. The studies were presented at the American Heart Association scientific sessions.
Both studies “add to our accumulating knowledge of the cardiovascular risks of marijuana,” Ersilia M. DeFilippis, MD, a cardiology fellow at Columbia University Irvine Medical Center, New York, who was not involved with this research, said in an interview.
Dr. DeFilippis and the two study authors say clinicians and patients need to be more aware of cardiovascular risks from smoking marijuana, and they call for more patient screening, counseling, and research.
Need for screening and counseling
Marijuana is a Schedule 1 controlled substance in the United States, which makes it illegal to conduct rigorous controlled trials of marijuana products. Existing knowledge is therefore based on observational studies, Dr. DeFilippis noted.
She was lead author of a review of marijuana use by patients with cardiovascular disease. The review was published in the Journal of the American College of Cardiology. An AHA scientific statement about marijuana and cardiovascular health was published in Circulation.
Both documents drew attention to risks from marijuana use in patients with cardiovascular disease.
Until more data are available, “I think it is absolutely critical” that cardiologists and general providers screen patients for marijuana use, “either at the time of their MI or ideally prior to that, when they are making a cardiovascular risk assessment,” said Dr. DeFilippis.
That is also the time to “counsel patients, especially those who have had an MI, about risks associated with continuing to use marijuana.”
Importantly, providers and patients need to be aware that “cannabinoids, through the cytochrome P450 system, can interact with well-known cardiovascular medications, which we know provide benefit in the post-MI period,” she added. “For example, marijuana can interfere with beta-blockers, statins, antiarrhythmics, and certain anticoagulants.”
Dr. Bhuva, a cardiology fellow with the Wright Center for Community Health, Scranton, Pa., said that it is “concerning” that “recurrent heart attacks and cardiac interventions [were] higher among cannabis users, even though they were younger and had fewer risk factors for heart disease.
“Spreading awareness regarding the potential risk of recurrent heart attacks in middle-aged, African American, and male cannabis users and screening them at an earlier age for potential risk factors of future heart attacks should be encouraged among clinicians,” he urged in a statement from the AHA.
Dr. Yoo, an internal medicine resident at the University of Michigan, Ann Arbor, pointed out that, in their study of patients who underwent PCI after MI or because they had coronary artery disease, those who smoked or vaped marijuana were younger and were more likely to be male. They were less likely to have traditional cardiovascular risk factors except for smoking tobacco, which was highly prevalent.
After propensity matching, patients who used marijuana had a 1.5-fold increased risk of in-hospital bleeding and an 11-fold higher risk for in-hospital stroke following PCI.
However, the absolute number of strokes in PCI was small, and the confidence interval was wide (indicating a large uncertainty), Dr. Yoo said in an interview.
These risks “should not deter patients from undergoing these [lifesaving] procedures,” he said; however, clinicians should be aware of these risks with marijuana use and should screen and counsel patients about this.
Hospitalized patients with prior MI
Dr. Bhuva and colleagues identified patients from the National Inpatient Sample who were hospitalized in the United States from 2007 to 2014 and who had experienced a prior MI and had undergone revascularization with PCI or coronary artery bypass grafting (CABG).
There were about 8 million hospital stays per year. The database did not specify the type of marijuana that patients used.
During the 8-year study period, many states legalized or decriminalized medical and/or recreational marijuana, and marijuana use increased steadily, from 0.2% to 0.7%.
Compared with nonusers, those who used marijuana were younger (median age, 53 vs. 72 years), and there were more men (77% vs. 62%) or Black persons (34% vs. 10%) (all P < .001). Fewer marijuana users had hypertension (72% vs. 75%), diabetes (24% vs. 33%), or dyslipidemia (51% vs. 58%) (all P < .001). More marijuana users underwent a repeat MI (67% vs. 41%).
On the other hand, marijuana users, who were younger and healthier than the other patients, were less likely to die during hospitalization for a recurrent MI (0.8% vs. 2.5%), and their hospital costs were lower.
The researchers acknowledged that study limitations include lack of information about marijuana type (smoked, edible, medicinal, or recreational) or dose, as well as the time from marijuana use to cardiac event.
In-Hospital outcomes after PCI
Dr. Yoo and colleagues analyzed data from patients who underwent PCI from Jan. 1, 2013, to Oct. 1, 2016, at Michigan’s 48 nonfederal hospitals, which are part of the Blue Cross Blue Shield Michigan Cardiovascular Consortium PCI registry.
In this cohort, 3,970 patients (3.5%) had smoked or vaped marijuana in the month prior to PCI, and 109,507 patients had not done so. The marijuana users were younger (mean age, 54 vs. 66 years) and were more likely to be male (79% vs. 67%) and to smoke cigarettes (73% vs. 27%).
They were less likely to have hypertension, type 2 diabetes, dyslipidemia, cerebrovascular disease, or prior CABG and were equally likely to have had a prior MI (36%).
Compared with nonusers, marijuana users were more likely to present with non–ST-elevation MI (30% vs. 23%) or ST-elevation MI (27% vs. 16%) and were less likely to present with angina.
Using propensity score matching, the researchers matched 3,803 marijuana users with the same number of nonusers.
In the matched cohort, patients who used marijuana had a greater risk of in-hospital bleeding (adjusted odds ratio, 1.54; 95% confidence interval, 1.20-1.97; P < .001) or stroke (aOR, 11.01; 95% CI, 1.32-91.67; P = .026) following PCI.
Marijuana users had a lower risk for acute kidney injury (2.2% vs. 2.9%; P = .007). Transfusion and mortality rates were similar in both groups.
The researchers acknowledged study limitations, including the fact that it did not include marijuana edibles, that the results may not be generalizable, and that marijuana use is now likely more common in Michigan following legalization of recreational marijuana in 2018.
Dr. Bhuva, Dr. Yoo, and Dr. DeFilippis have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
From AHA 2020
Cardiac arrest in COVID-19 pandemic: ‘Survival is possible’
In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.
A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.
Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.
Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.
“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.
“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”
Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.
“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”
“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.
“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”
“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.
“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
Out-of-hospital cardiac arrest, March 2019 vs. March 2020
Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.
In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.
They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.
There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.
The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).
Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).
The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).
In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).
This drop in survival was greater in communities with moderate to high COVID-19 mortality.
These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.
Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.
Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.
For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”
“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.
“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.
In-hospital cardiac arrest, March Through May 2020
The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.
“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”
To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.
They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).
Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.
There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).
“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”
“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.
Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”
Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.
A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.
Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.
Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.
“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.
“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”
Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.
“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”
“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.
“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”
“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.
“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
Out-of-hospital cardiac arrest, March 2019 vs. March 2020
Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.
In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.
They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.
There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.
The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).
Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).
The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).
In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).
This drop in survival was greater in communities with moderate to high COVID-19 mortality.
These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.
Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.
Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.
For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”
“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.
“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.
In-hospital cardiac arrest, March Through May 2020
The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.
“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”
To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.
They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).
Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.
There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).
“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”
“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.
Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”
Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.
A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.
Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.
Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.
“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.
“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”
Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.
“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”
“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.
“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”
“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.
“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
Out-of-hospital cardiac arrest, March 2019 vs. March 2020
Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.
In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.
They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.
There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.
The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).
Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).
The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).
In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).
This drop in survival was greater in communities with moderate to high COVID-19 mortality.
These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.
Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.
Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.
For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”
“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.
“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.
In-hospital cardiac arrest, March Through May 2020
The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.
“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”
To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.
They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).
Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.
There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).
“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”
“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.
Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”
Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AHA 2020
In those with obesity, will losing weight cut COVID-19 severity?
As study after study piles up showing that those with obesity who become infected with SARS-CoV-2 are more likely to have severe disease, several experts gave advice for clinicians and patients during the virtual ObesityWeek Interactive 2020 meeting.
Pichamol Jirapinyo, MD, MPH, associate director of bariatric endoscopy at Brigham and Women’s Hospital, Boston, presented a study on those with obesity from New England hospitals which adds to the evidence that this is “a vulnerable population for COVID-19, like elderly or immunocompromised people,” Dr. Jirapinyo said in an interview.
These findings reinforce the need for clinicians to be “more aware of complications of obesity and refer earlier for treatment,” she added.
One audience member wanted to know if there are data showing whether people with a body mass index (BMI) above 35 kg/m2 who successfully lose weight subsequently have lower rates of hospitalization, ICU admission, and death if they become infected with SARS-CoV-2.
Dr. Jirapinyo said she is not aware of any such studies, but anecdotally, two of her patients who had endoscopic sleeve gastroplasty last fall (whose BMI dropped from about 38 to 30) and later became infected with COVID-19 had mild symptoms.
But David A. Kass, MD, director, Institute of CardioScience at Johns Hopkins University, Baltimore, cautioned that
“Whether this gets reversed by weight loss is an attractive hypothesis, but at this point, it’s still a hypothesis,” he stressed.
Changes to immunity, inflammatory signaling in obesity
“There must be north of 600 or more studies by now with this message that obesity – particularly severe obesity with a BMI of 35 and higher – is a strong independent risk factor for worse COVID-19 outcome,” Dr. Kass emphasized.
“[COVID-19] revealed to the public in a somewhat dramatic fashion that being very obese does put one at higher risk of this disease being more debilitating and even fatal,” he added.
“Before this pandemic, many viewed obesity as only a problem if you have the other associated diseases – hypertension, diabetes, heart disease, atherosclerosis, obstructive sleep apnea, etc.”
“What was not as appreciated is that marked obesity changes the body in various ways all by itself – altering metabolism, inflammatory signaling, immune surveillance, and responsiveness (including a less robust response to vaccines that has been written about as well).”
“This is a bit like having a genetic abnormality that makes you at higher risk for getting, say, cancer,” he explained.
“It is there, it is real, it has an impact – but it still does take other stresses to reveal the risk potential. COVID-19 did that with obesity,” he said.
Latest study on effect of obesity, diabetes on COVID-19 severity
The study presented by Dr. Jirapinyo and colleagues identified 1,680 patients with COVID-19 at six hospitals in March 2020. Patients were a mean age of 51 years, had a mean BMI of 29.4, and 39% had obesity. Patients who required hospitalization were more likely to have obesity (46% vs. 35%; P < .0001).
Obesity was a significant risk factor for hospitalization (odds ratio, 1.7), ICU admission (OR, 1.8), and intubation (OR, 1.8; all P < .001), after controlling for age, sex, cardiovascular, pulmonary, liver, and kidney disease, and cancer.
Compared with having a normal weight, having severe obesity was also associated with roughly threefold higher risks of ICU admission and intubation – after controlling for major comorbidities.
Pandemic focuses minds on obesity prevention, treatment
Naveed Sattar, MD, PhD, said in an interview that these latest findings are “highly consistent with other studies that point to excess adiposity as a potential modifiable risk factor for more severe COVID-19.”
It “also strongly suggests that if people are worried about their risk for COVID-19 and want to improve their chances of a milder outcome, then it is reasonable to encourage them to make sustainable lifestyle changes that may lessen weight and improve their fitness levels,” said Dr. Sattar, professor of metabolic medicine, University of Glasgow.
“But of course, the big worry,” he added, “is that many are putting on weight due to lockdowns, less commuting to work, anxiety, and overeating and drinking, etc., so that many are struggling, and especially those at highest risk, such as those living in more overcrowded housing, etc. By contrast, more advantaged folk may have an easier time to improve lifestyles.”
The pandemic highlights that “we need a concerted effort on obesity prevention and treatment,” according to Dr. Sattar.
“For years we have realized links between obesity and chronic cardiometabolic conditions,” he said, “but to think excess weight may also be detrimental to acute effects of a novel virus running amok in the world has focused minds on obesity in a manner not seen before.
“Whether these new painful learnings lead to a more determined effort in countries to improve the obesogenic environment or to place more resources into prevention and management of obesity remains to be seen,” he said.
Increased inquiries about bariatric surgery following COVID-19
Meanwhile, Matthew M. Hutter, MD, MPH, president, American Society for Metabolic and Bariatric Surgery, said in an interview that “COVID-19 and studies like this are now making many aware that obesity is not just a lifestyle choice or a cosmetic issue, but “a disease that needs to be taken seriously” and treated.
“Metabolic and bariatric surgery is a very safe and effective treatment for persons with obesity with a BMI >40 kg/m2 or BMI >35 kg/m2 and related diseases like diabetes, hypertension, sleep apnea, reflux, back pain, and many others,” added Dr. Hutter, who is also professor of surgery, Harvard Medical School, Boston.
“Recently, some metabolic and bariatric centers have seen an increase in patients considering surgery,” he said. “Some say that COVID-19 has made them realize they need to do something to be healthier.”
“Currently, less than 1% of those who could benefit from surgery are actually having” it each year, Dr. Hutter noted, “and I think there are many who should seriously consider surgery to be healthier, live longer, and live better.”
This article first appeared on Medscape.com.
As study after study piles up showing that those with obesity who become infected with SARS-CoV-2 are more likely to have severe disease, several experts gave advice for clinicians and patients during the virtual ObesityWeek Interactive 2020 meeting.
Pichamol Jirapinyo, MD, MPH, associate director of bariatric endoscopy at Brigham and Women’s Hospital, Boston, presented a study on those with obesity from New England hospitals which adds to the evidence that this is “a vulnerable population for COVID-19, like elderly or immunocompromised people,” Dr. Jirapinyo said in an interview.
These findings reinforce the need for clinicians to be “more aware of complications of obesity and refer earlier for treatment,” she added.
One audience member wanted to know if there are data showing whether people with a body mass index (BMI) above 35 kg/m2 who successfully lose weight subsequently have lower rates of hospitalization, ICU admission, and death if they become infected with SARS-CoV-2.
Dr. Jirapinyo said she is not aware of any such studies, but anecdotally, two of her patients who had endoscopic sleeve gastroplasty last fall (whose BMI dropped from about 38 to 30) and later became infected with COVID-19 had mild symptoms.
But David A. Kass, MD, director, Institute of CardioScience at Johns Hopkins University, Baltimore, cautioned that
“Whether this gets reversed by weight loss is an attractive hypothesis, but at this point, it’s still a hypothesis,” he stressed.
Changes to immunity, inflammatory signaling in obesity
“There must be north of 600 or more studies by now with this message that obesity – particularly severe obesity with a BMI of 35 and higher – is a strong independent risk factor for worse COVID-19 outcome,” Dr. Kass emphasized.
“[COVID-19] revealed to the public in a somewhat dramatic fashion that being very obese does put one at higher risk of this disease being more debilitating and even fatal,” he added.
“Before this pandemic, many viewed obesity as only a problem if you have the other associated diseases – hypertension, diabetes, heart disease, atherosclerosis, obstructive sleep apnea, etc.”
“What was not as appreciated is that marked obesity changes the body in various ways all by itself – altering metabolism, inflammatory signaling, immune surveillance, and responsiveness (including a less robust response to vaccines that has been written about as well).”
“This is a bit like having a genetic abnormality that makes you at higher risk for getting, say, cancer,” he explained.
“It is there, it is real, it has an impact – but it still does take other stresses to reveal the risk potential. COVID-19 did that with obesity,” he said.
Latest study on effect of obesity, diabetes on COVID-19 severity
The study presented by Dr. Jirapinyo and colleagues identified 1,680 patients with COVID-19 at six hospitals in March 2020. Patients were a mean age of 51 years, had a mean BMI of 29.4, and 39% had obesity. Patients who required hospitalization were more likely to have obesity (46% vs. 35%; P < .0001).
Obesity was a significant risk factor for hospitalization (odds ratio, 1.7), ICU admission (OR, 1.8), and intubation (OR, 1.8; all P < .001), after controlling for age, sex, cardiovascular, pulmonary, liver, and kidney disease, and cancer.
Compared with having a normal weight, having severe obesity was also associated with roughly threefold higher risks of ICU admission and intubation – after controlling for major comorbidities.
Pandemic focuses minds on obesity prevention, treatment
Naveed Sattar, MD, PhD, said in an interview that these latest findings are “highly consistent with other studies that point to excess adiposity as a potential modifiable risk factor for more severe COVID-19.”
It “also strongly suggests that if people are worried about their risk for COVID-19 and want to improve their chances of a milder outcome, then it is reasonable to encourage them to make sustainable lifestyle changes that may lessen weight and improve their fitness levels,” said Dr. Sattar, professor of metabolic medicine, University of Glasgow.
“But of course, the big worry,” he added, “is that many are putting on weight due to lockdowns, less commuting to work, anxiety, and overeating and drinking, etc., so that many are struggling, and especially those at highest risk, such as those living in more overcrowded housing, etc. By contrast, more advantaged folk may have an easier time to improve lifestyles.”
The pandemic highlights that “we need a concerted effort on obesity prevention and treatment,” according to Dr. Sattar.
“For years we have realized links between obesity and chronic cardiometabolic conditions,” he said, “but to think excess weight may also be detrimental to acute effects of a novel virus running amok in the world has focused minds on obesity in a manner not seen before.
“Whether these new painful learnings lead to a more determined effort in countries to improve the obesogenic environment or to place more resources into prevention and management of obesity remains to be seen,” he said.
Increased inquiries about bariatric surgery following COVID-19
Meanwhile, Matthew M. Hutter, MD, MPH, president, American Society for Metabolic and Bariatric Surgery, said in an interview that “COVID-19 and studies like this are now making many aware that obesity is not just a lifestyle choice or a cosmetic issue, but “a disease that needs to be taken seriously” and treated.
“Metabolic and bariatric surgery is a very safe and effective treatment for persons with obesity with a BMI >40 kg/m2 or BMI >35 kg/m2 and related diseases like diabetes, hypertension, sleep apnea, reflux, back pain, and many others,” added Dr. Hutter, who is also professor of surgery, Harvard Medical School, Boston.
“Recently, some metabolic and bariatric centers have seen an increase in patients considering surgery,” he said. “Some say that COVID-19 has made them realize they need to do something to be healthier.”
“Currently, less than 1% of those who could benefit from surgery are actually having” it each year, Dr. Hutter noted, “and I think there are many who should seriously consider surgery to be healthier, live longer, and live better.”
This article first appeared on Medscape.com.
As study after study piles up showing that those with obesity who become infected with SARS-CoV-2 are more likely to have severe disease, several experts gave advice for clinicians and patients during the virtual ObesityWeek Interactive 2020 meeting.
Pichamol Jirapinyo, MD, MPH, associate director of bariatric endoscopy at Brigham and Women’s Hospital, Boston, presented a study on those with obesity from New England hospitals which adds to the evidence that this is “a vulnerable population for COVID-19, like elderly or immunocompromised people,” Dr. Jirapinyo said in an interview.
These findings reinforce the need for clinicians to be “more aware of complications of obesity and refer earlier for treatment,” she added.
One audience member wanted to know if there are data showing whether people with a body mass index (BMI) above 35 kg/m2 who successfully lose weight subsequently have lower rates of hospitalization, ICU admission, and death if they become infected with SARS-CoV-2.
Dr. Jirapinyo said she is not aware of any such studies, but anecdotally, two of her patients who had endoscopic sleeve gastroplasty last fall (whose BMI dropped from about 38 to 30) and later became infected with COVID-19 had mild symptoms.
But David A. Kass, MD, director, Institute of CardioScience at Johns Hopkins University, Baltimore, cautioned that
“Whether this gets reversed by weight loss is an attractive hypothesis, but at this point, it’s still a hypothesis,” he stressed.
Changes to immunity, inflammatory signaling in obesity
“There must be north of 600 or more studies by now with this message that obesity – particularly severe obesity with a BMI of 35 and higher – is a strong independent risk factor for worse COVID-19 outcome,” Dr. Kass emphasized.
“[COVID-19] revealed to the public in a somewhat dramatic fashion that being very obese does put one at higher risk of this disease being more debilitating and even fatal,” he added.
“Before this pandemic, many viewed obesity as only a problem if you have the other associated diseases – hypertension, diabetes, heart disease, atherosclerosis, obstructive sleep apnea, etc.”
“What was not as appreciated is that marked obesity changes the body in various ways all by itself – altering metabolism, inflammatory signaling, immune surveillance, and responsiveness (including a less robust response to vaccines that has been written about as well).”
“This is a bit like having a genetic abnormality that makes you at higher risk for getting, say, cancer,” he explained.
“It is there, it is real, it has an impact – but it still does take other stresses to reveal the risk potential. COVID-19 did that with obesity,” he said.
Latest study on effect of obesity, diabetes on COVID-19 severity
The study presented by Dr. Jirapinyo and colleagues identified 1,680 patients with COVID-19 at six hospitals in March 2020. Patients were a mean age of 51 years, had a mean BMI of 29.4, and 39% had obesity. Patients who required hospitalization were more likely to have obesity (46% vs. 35%; P < .0001).
Obesity was a significant risk factor for hospitalization (odds ratio, 1.7), ICU admission (OR, 1.8), and intubation (OR, 1.8; all P < .001), after controlling for age, sex, cardiovascular, pulmonary, liver, and kidney disease, and cancer.
Compared with having a normal weight, having severe obesity was also associated with roughly threefold higher risks of ICU admission and intubation – after controlling for major comorbidities.
Pandemic focuses minds on obesity prevention, treatment
Naveed Sattar, MD, PhD, said in an interview that these latest findings are “highly consistent with other studies that point to excess adiposity as a potential modifiable risk factor for more severe COVID-19.”
It “also strongly suggests that if people are worried about their risk for COVID-19 and want to improve their chances of a milder outcome, then it is reasonable to encourage them to make sustainable lifestyle changes that may lessen weight and improve their fitness levels,” said Dr. Sattar, professor of metabolic medicine, University of Glasgow.
“But of course, the big worry,” he added, “is that many are putting on weight due to lockdowns, less commuting to work, anxiety, and overeating and drinking, etc., so that many are struggling, and especially those at highest risk, such as those living in more overcrowded housing, etc. By contrast, more advantaged folk may have an easier time to improve lifestyles.”
The pandemic highlights that “we need a concerted effort on obesity prevention and treatment,” according to Dr. Sattar.
“For years we have realized links between obesity and chronic cardiometabolic conditions,” he said, “but to think excess weight may also be detrimental to acute effects of a novel virus running amok in the world has focused minds on obesity in a manner not seen before.
“Whether these new painful learnings lead to a more determined effort in countries to improve the obesogenic environment or to place more resources into prevention and management of obesity remains to be seen,” he said.
Increased inquiries about bariatric surgery following COVID-19
Meanwhile, Matthew M. Hutter, MD, MPH, president, American Society for Metabolic and Bariatric Surgery, said in an interview that “COVID-19 and studies like this are now making many aware that obesity is not just a lifestyle choice or a cosmetic issue, but “a disease that needs to be taken seriously” and treated.
“Metabolic and bariatric surgery is a very safe and effective treatment for persons with obesity with a BMI >40 kg/m2 or BMI >35 kg/m2 and related diseases like diabetes, hypertension, sleep apnea, reflux, back pain, and many others,” added Dr. Hutter, who is also professor of surgery, Harvard Medical School, Boston.
“Recently, some metabolic and bariatric centers have seen an increase in patients considering surgery,” he said. “Some say that COVID-19 has made them realize they need to do something to be healthier.”
“Currently, less than 1% of those who could benefit from surgery are actually having” it each year, Dr. Hutter noted, “and I think there are many who should seriously consider surgery to be healthier, live longer, and live better.”
This article first appeared on Medscape.com.
Major breakthrough? Average 10% weight loss with semaglutide
In a phase 3 trial where all participants received intensive behavior therapy, investigational 2.4-mg once-weekly subcutaneous semaglutide (Novo Nordisk) resulted in a 10.3% greater average weight loss than placebo over a period of 68 weeks.
If approved, this medication could be a “potential major breakthrough” in obesity management, the investigators suggested. But other experts urged caution, as cost and uptake are important considerations.
‘Potential weight loss that patients would be happy with’
Thomas A. Wadden, PhD, presented results from the study of 611 adults with overweight or obesity but no diabetes at the virtual ObesityWeek® Interactive 2020 meeting.
“Perhaps even more impressive was the finding that 75% of patients lost 10% or more of baseline body weight,” said Dr. Wadden, of the department of psychiatry at the University of Pennsylvania, Philadelphia.
Moreover, in this trial of semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist that is approved for treating type 2 diabetes at a weekly subcutaneous dose of 1 mg, but is being investigated at the higher dose for weight loss – 55% of patients lost ≥15% of their initial weight, and 36% lost ≥20% of their initial weight.
“These large categorical weight losses – particularly of 15% and 20% of initial weight – are potentially a major breakthrough in the management of obesity,” Dr. Wadden said in an interview.
Weight losses of this size, he added, “should confer greater improvements in cardiometabolic risk factors (such as hypertension, sleep apnea, and type 2 diabetes) as compared with losses of 5%-10% achieved with current behavioral or pharmacological approaches.” And patients are generally not satisfied with losses of less than 10% of initial weight when participating in intensive behavior programs or taking weight-loss medications.
Now, “the larger categorical weight losses will mean that a greater number of patients with obesity will be able to achieve a weight loss with which they are ... happy,” Dr. Wadden said in an interview.
According to Louis J. Aronne, MD, Weill Professor of Metabolic Research, Weill Cornell Medicine, New York, who is an investigator for another trial of semaglutide: “Even though it has the same mechanism of action [as liraglutide], the weight loss is two or more times greater [with semaglutide]. In my opinion, it’s really going to be a major advance in the treatment of obesity.”
In the discussion that followed the virtual presentation, one attendee asked about potential weight regain if a patient stopped taking the drug. Based on experience with another subcutaneous injectable GLP-1 receptor agonist, liraglutide (Saxenda), already approved for obesity, it may be that taking medicine for chronic overweight may become like taking a statin for elevated cholesterol, said Dr. Wadden.
Novo Nordisk has now completed the four trials in the STEP (Semaglutide Treatment Effect in People With Obesity) global phase 3 clinical development program, and plans to file applications with the Food and Drug Administration later this year and with the European Medicines Agency in early 2021 for review of semaglutide 2.4 mg for weight management.
“Fundamental issues need to be figured out”
Invited to comment, Scott Kahan, MD, said: “This is impressive data, confirming that semaglutide, particularly when used in concert with evidence-based counseling, is a highly effective agent for obesity management.”
However, “the real question, though, is what comes next,” stressed Dr. Kahan, director of the National Center for Weight and Wellness, Washington, DC.
“Will it be approved by the U.S. FDA? I believe so,” he said in an interview. “Yet we already have several effective obesity medications approved over the past decade – all of which are rarely used and therefore make little impact for patients in the real world.”
“Will there be insurance coverage, and therefore practical access for those who could most benefit?” he continued. “Will prescribers counsel their patients about obesity management, including the use of effective medications? Will patients utilize available options?”
“These and other fundamental issues must be figured out before we anoint any treatment option as a meaningful step forward, let alone a transformative development,” according to Dr. Kahan.
Similarly, Irl B. Hirsch, MD, stressed that, should this medication be approved for weight loss, cost would be a major factor in its uptake.
“I’m old enough to recall when we started using lovastatin in the late 1980s,” Dr. Hirsch, professor of medicine, University of Washington Medicine Diabetes Institute, Seattle, said in an interview.
“We used it without the type of evidence of statin use we have today. A pill, but in those days the statins were expensive. But over time, the evidence for statins grew and over the next 15 years it was quite clear that for both primary prevention (for those with diabetes) and secondary intervention these drugs needed to be used by millions of people. These recommendations became easier once the drugs became generic.
“Will the same thing happen for GLP-1 agonists? The problem is we need both ‘hard-outcome data’ [such as 3-point major adverse cardiovascular events] and more reasonable cost before we see this expanding to an entire population.
“In the future perhaps we could have a biosimilar GLP-1 agonist that would be more affordable than what we pay now, but even before that we need agreement from our reimbursement thought leaders that our society should reimburse these agents.
“My thinking now is the cost-benefit could be favorable, but this is all dependent on what happens to the cost of the drugs over time,” he said.
Additive effect of intensive behavior therapy plus medication
Dr. Wadden explained that intensive behavioral therapy “provides 14 or more counseling sessions in 6 months to modify diet and physical activity, through the patients’ use of behavioral strategies (such as keeping daily food and activity diaries).”
Such programs typically produce mean weight loss of 5%-8% of initial weight; less frequent (e.g., monthly) programs typically produce weight loss of only 1%-3%.
Prior studies suggest that intensive behavioral therapy and medication have additive effects. To investigate this, Dr. Wadden and colleagues randomized 611 adults (81% women) who were a mean age of 46 years and had a mean body mass index of 38 kg/m2.
All participants received 30 intensive behavior therapy sessions provided by a registered dietitian (or other qualified provider), which typically lasted 20-30 minutes and were given weekly for 12 weeks, every other week for the next 12 weeks, and then monthly.
The dietitian gave participants behavioral strategies to help them adhere to diet and physical activity goals.
During the first 8 weeks, participants were provided with a 1,000-1,200 kcal/day meal replacement diet that included liquid shakes, meal bars, and prepared entrees designed to facilitate a large initial weight loss.
They then transitioned to a diet of conventional foods (of their choosing), with a goal of 1,200-1,800 kcal/day based on body weight.
The physical activity goal was 100 minutes/week of walking or other aerobic activity in the first month, building up to 200 minutes/week by month 6.
‘More effective than current FDA-approved weight-loss medications’
At week 68, mean body weight decreased from baseline by 16.0% in the semaglutide group versus 5.7% in the placebo group (P < .0001).
In this trial, where all participants received extensive intensive behavior therapy, more participants had weight loss ≥5%, ≥10%, ≥15%, and ≥20% of their initial weight with semaglutide versus placebo (87% vs. 48%; 75% vs. 27%; 56% vs. 13%; 36% vs. 4%, respectively; all P < .0001).
From baseline to week 68, the proportion of participants with prediabetes decreased from 48% to 7% in the semaglutide group and from 53% to 26% in the placebo group.
Patients who received semaglutide had greater improvements in lipids, too.
Although the weight loss was 10.3% (10.6 kg) greater with semaglutide, Dr. Wadden noted, “additional studies have shown this net benefit to be as great as 11%-12%, which would make semaglutide 2.4 mg more effective than current [FDA-approved] weight-loss medications.”
“Naltrexone-bupropion (Contrave) with lifestyle counseling, for example,” he continued, “produces a loss that is 5 kg greater than lifestyle counseling plus placebo, liraglutide 3.0 mg (Saxenda) a loss 5.3 kg greater than placebo, and phentermine-topiramate (Qsymia) a loss that is 8.8 kg greater than placebo.”
Semaglutide was well tolerated. Gastrointestinal adverse events, the most common type, occurred in 83% of patients in the semaglutide group and 63% of patients in the placebo group.
Nausea, as well as constipation and diarrhea, are common in medications that increase GLP-1 levels, Dr. Wadden noted. Side effects can be managed by slowly increasing the medication dose over 4 months.
Dr. Wadden expects that, if approved, semaglutide 2.4 mg subcutaneous once-weekly will be recommended as an adjunct to a reduced calorie diet and increased physical activity. Additional studies suggest that monthly counseling should be sufficient to obtain similar weight losses as those seen in the current trial, which had more intensive counseling.
As well as being approved as a weekly subcutaneous injectable treatment for type 2 diabetes, semaglutide is also approved as an once-daily oral agent for the same indication (Rybelsus, Novo Nordisk) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
Dr. Wadden serves on scientific advisory boards for Novo Nordisk and WW (formerly Weight Watchers), and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. Dr. Aronne is an investigator in a long-term trial of semaglutide and has served on scientific advisory boards for Novo Nordisk in the past. He also has other industry relationships that are not related to semaglutide.
A version of this article originally appeared on Medscape.com.
In a phase 3 trial where all participants received intensive behavior therapy, investigational 2.4-mg once-weekly subcutaneous semaglutide (Novo Nordisk) resulted in a 10.3% greater average weight loss than placebo over a period of 68 weeks.
If approved, this medication could be a “potential major breakthrough” in obesity management, the investigators suggested. But other experts urged caution, as cost and uptake are important considerations.
‘Potential weight loss that patients would be happy with’
Thomas A. Wadden, PhD, presented results from the study of 611 adults with overweight or obesity but no diabetes at the virtual ObesityWeek® Interactive 2020 meeting.
“Perhaps even more impressive was the finding that 75% of patients lost 10% or more of baseline body weight,” said Dr. Wadden, of the department of psychiatry at the University of Pennsylvania, Philadelphia.
Moreover, in this trial of semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist that is approved for treating type 2 diabetes at a weekly subcutaneous dose of 1 mg, but is being investigated at the higher dose for weight loss – 55% of patients lost ≥15% of their initial weight, and 36% lost ≥20% of their initial weight.
“These large categorical weight losses – particularly of 15% and 20% of initial weight – are potentially a major breakthrough in the management of obesity,” Dr. Wadden said in an interview.
Weight losses of this size, he added, “should confer greater improvements in cardiometabolic risk factors (such as hypertension, sleep apnea, and type 2 diabetes) as compared with losses of 5%-10% achieved with current behavioral or pharmacological approaches.” And patients are generally not satisfied with losses of less than 10% of initial weight when participating in intensive behavior programs or taking weight-loss medications.
Now, “the larger categorical weight losses will mean that a greater number of patients with obesity will be able to achieve a weight loss with which they are ... happy,” Dr. Wadden said in an interview.
According to Louis J. Aronne, MD, Weill Professor of Metabolic Research, Weill Cornell Medicine, New York, who is an investigator for another trial of semaglutide: “Even though it has the same mechanism of action [as liraglutide], the weight loss is two or more times greater [with semaglutide]. In my opinion, it’s really going to be a major advance in the treatment of obesity.”
In the discussion that followed the virtual presentation, one attendee asked about potential weight regain if a patient stopped taking the drug. Based on experience with another subcutaneous injectable GLP-1 receptor agonist, liraglutide (Saxenda), already approved for obesity, it may be that taking medicine for chronic overweight may become like taking a statin for elevated cholesterol, said Dr. Wadden.
Novo Nordisk has now completed the four trials in the STEP (Semaglutide Treatment Effect in People With Obesity) global phase 3 clinical development program, and plans to file applications with the Food and Drug Administration later this year and with the European Medicines Agency in early 2021 for review of semaglutide 2.4 mg for weight management.
“Fundamental issues need to be figured out”
Invited to comment, Scott Kahan, MD, said: “This is impressive data, confirming that semaglutide, particularly when used in concert with evidence-based counseling, is a highly effective agent for obesity management.”
However, “the real question, though, is what comes next,” stressed Dr. Kahan, director of the National Center for Weight and Wellness, Washington, DC.
“Will it be approved by the U.S. FDA? I believe so,” he said in an interview. “Yet we already have several effective obesity medications approved over the past decade – all of which are rarely used and therefore make little impact for patients in the real world.”
“Will there be insurance coverage, and therefore practical access for those who could most benefit?” he continued. “Will prescribers counsel their patients about obesity management, including the use of effective medications? Will patients utilize available options?”
“These and other fundamental issues must be figured out before we anoint any treatment option as a meaningful step forward, let alone a transformative development,” according to Dr. Kahan.
Similarly, Irl B. Hirsch, MD, stressed that, should this medication be approved for weight loss, cost would be a major factor in its uptake.
“I’m old enough to recall when we started using lovastatin in the late 1980s,” Dr. Hirsch, professor of medicine, University of Washington Medicine Diabetes Institute, Seattle, said in an interview.
“We used it without the type of evidence of statin use we have today. A pill, but in those days the statins were expensive. But over time, the evidence for statins grew and over the next 15 years it was quite clear that for both primary prevention (for those with diabetes) and secondary intervention these drugs needed to be used by millions of people. These recommendations became easier once the drugs became generic.
“Will the same thing happen for GLP-1 agonists? The problem is we need both ‘hard-outcome data’ [such as 3-point major adverse cardiovascular events] and more reasonable cost before we see this expanding to an entire population.
“In the future perhaps we could have a biosimilar GLP-1 agonist that would be more affordable than what we pay now, but even before that we need agreement from our reimbursement thought leaders that our society should reimburse these agents.
“My thinking now is the cost-benefit could be favorable, but this is all dependent on what happens to the cost of the drugs over time,” he said.
Additive effect of intensive behavior therapy plus medication
Dr. Wadden explained that intensive behavioral therapy “provides 14 or more counseling sessions in 6 months to modify diet and physical activity, through the patients’ use of behavioral strategies (such as keeping daily food and activity diaries).”
Such programs typically produce mean weight loss of 5%-8% of initial weight; less frequent (e.g., monthly) programs typically produce weight loss of only 1%-3%.
Prior studies suggest that intensive behavioral therapy and medication have additive effects. To investigate this, Dr. Wadden and colleagues randomized 611 adults (81% women) who were a mean age of 46 years and had a mean body mass index of 38 kg/m2.
All participants received 30 intensive behavior therapy sessions provided by a registered dietitian (or other qualified provider), which typically lasted 20-30 minutes and were given weekly for 12 weeks, every other week for the next 12 weeks, and then monthly.
The dietitian gave participants behavioral strategies to help them adhere to diet and physical activity goals.
During the first 8 weeks, participants were provided with a 1,000-1,200 kcal/day meal replacement diet that included liquid shakes, meal bars, and prepared entrees designed to facilitate a large initial weight loss.
They then transitioned to a diet of conventional foods (of their choosing), with a goal of 1,200-1,800 kcal/day based on body weight.
The physical activity goal was 100 minutes/week of walking or other aerobic activity in the first month, building up to 200 minutes/week by month 6.
‘More effective than current FDA-approved weight-loss medications’
At week 68, mean body weight decreased from baseline by 16.0% in the semaglutide group versus 5.7% in the placebo group (P < .0001).
In this trial, where all participants received extensive intensive behavior therapy, more participants had weight loss ≥5%, ≥10%, ≥15%, and ≥20% of their initial weight with semaglutide versus placebo (87% vs. 48%; 75% vs. 27%; 56% vs. 13%; 36% vs. 4%, respectively; all P < .0001).
From baseline to week 68, the proportion of participants with prediabetes decreased from 48% to 7% in the semaglutide group and from 53% to 26% in the placebo group.
Patients who received semaglutide had greater improvements in lipids, too.
Although the weight loss was 10.3% (10.6 kg) greater with semaglutide, Dr. Wadden noted, “additional studies have shown this net benefit to be as great as 11%-12%, which would make semaglutide 2.4 mg more effective than current [FDA-approved] weight-loss medications.”
“Naltrexone-bupropion (Contrave) with lifestyle counseling, for example,” he continued, “produces a loss that is 5 kg greater than lifestyle counseling plus placebo, liraglutide 3.0 mg (Saxenda) a loss 5.3 kg greater than placebo, and phentermine-topiramate (Qsymia) a loss that is 8.8 kg greater than placebo.”
Semaglutide was well tolerated. Gastrointestinal adverse events, the most common type, occurred in 83% of patients in the semaglutide group and 63% of patients in the placebo group.
Nausea, as well as constipation and diarrhea, are common in medications that increase GLP-1 levels, Dr. Wadden noted. Side effects can be managed by slowly increasing the medication dose over 4 months.
Dr. Wadden expects that, if approved, semaglutide 2.4 mg subcutaneous once-weekly will be recommended as an adjunct to a reduced calorie diet and increased physical activity. Additional studies suggest that monthly counseling should be sufficient to obtain similar weight losses as those seen in the current trial, which had more intensive counseling.
As well as being approved as a weekly subcutaneous injectable treatment for type 2 diabetes, semaglutide is also approved as an once-daily oral agent for the same indication (Rybelsus, Novo Nordisk) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
Dr. Wadden serves on scientific advisory boards for Novo Nordisk and WW (formerly Weight Watchers), and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. Dr. Aronne is an investigator in a long-term trial of semaglutide and has served on scientific advisory boards for Novo Nordisk in the past. He also has other industry relationships that are not related to semaglutide.
A version of this article originally appeared on Medscape.com.
In a phase 3 trial where all participants received intensive behavior therapy, investigational 2.4-mg once-weekly subcutaneous semaglutide (Novo Nordisk) resulted in a 10.3% greater average weight loss than placebo over a period of 68 weeks.
If approved, this medication could be a “potential major breakthrough” in obesity management, the investigators suggested. But other experts urged caution, as cost and uptake are important considerations.
‘Potential weight loss that patients would be happy with’
Thomas A. Wadden, PhD, presented results from the study of 611 adults with overweight or obesity but no diabetes at the virtual ObesityWeek® Interactive 2020 meeting.
“Perhaps even more impressive was the finding that 75% of patients lost 10% or more of baseline body weight,” said Dr. Wadden, of the department of psychiatry at the University of Pennsylvania, Philadelphia.
Moreover, in this trial of semaglutide, a glucagonlike peptide–1 (GLP-1) receptor agonist that is approved for treating type 2 diabetes at a weekly subcutaneous dose of 1 mg, but is being investigated at the higher dose for weight loss – 55% of patients lost ≥15% of their initial weight, and 36% lost ≥20% of their initial weight.
“These large categorical weight losses – particularly of 15% and 20% of initial weight – are potentially a major breakthrough in the management of obesity,” Dr. Wadden said in an interview.
Weight losses of this size, he added, “should confer greater improvements in cardiometabolic risk factors (such as hypertension, sleep apnea, and type 2 diabetes) as compared with losses of 5%-10% achieved with current behavioral or pharmacological approaches.” And patients are generally not satisfied with losses of less than 10% of initial weight when participating in intensive behavior programs or taking weight-loss medications.
Now, “the larger categorical weight losses will mean that a greater number of patients with obesity will be able to achieve a weight loss with which they are ... happy,” Dr. Wadden said in an interview.
According to Louis J. Aronne, MD, Weill Professor of Metabolic Research, Weill Cornell Medicine, New York, who is an investigator for another trial of semaglutide: “Even though it has the same mechanism of action [as liraglutide], the weight loss is two or more times greater [with semaglutide]. In my opinion, it’s really going to be a major advance in the treatment of obesity.”
In the discussion that followed the virtual presentation, one attendee asked about potential weight regain if a patient stopped taking the drug. Based on experience with another subcutaneous injectable GLP-1 receptor agonist, liraglutide (Saxenda), already approved for obesity, it may be that taking medicine for chronic overweight may become like taking a statin for elevated cholesterol, said Dr. Wadden.
Novo Nordisk has now completed the four trials in the STEP (Semaglutide Treatment Effect in People With Obesity) global phase 3 clinical development program, and plans to file applications with the Food and Drug Administration later this year and with the European Medicines Agency in early 2021 for review of semaglutide 2.4 mg for weight management.
“Fundamental issues need to be figured out”
Invited to comment, Scott Kahan, MD, said: “This is impressive data, confirming that semaglutide, particularly when used in concert with evidence-based counseling, is a highly effective agent for obesity management.”
However, “the real question, though, is what comes next,” stressed Dr. Kahan, director of the National Center for Weight and Wellness, Washington, DC.
“Will it be approved by the U.S. FDA? I believe so,” he said in an interview. “Yet we already have several effective obesity medications approved over the past decade – all of which are rarely used and therefore make little impact for patients in the real world.”
“Will there be insurance coverage, and therefore practical access for those who could most benefit?” he continued. “Will prescribers counsel their patients about obesity management, including the use of effective medications? Will patients utilize available options?”
“These and other fundamental issues must be figured out before we anoint any treatment option as a meaningful step forward, let alone a transformative development,” according to Dr. Kahan.
Similarly, Irl B. Hirsch, MD, stressed that, should this medication be approved for weight loss, cost would be a major factor in its uptake.
“I’m old enough to recall when we started using lovastatin in the late 1980s,” Dr. Hirsch, professor of medicine, University of Washington Medicine Diabetes Institute, Seattle, said in an interview.
“We used it without the type of evidence of statin use we have today. A pill, but in those days the statins were expensive. But over time, the evidence for statins grew and over the next 15 years it was quite clear that for both primary prevention (for those with diabetes) and secondary intervention these drugs needed to be used by millions of people. These recommendations became easier once the drugs became generic.
“Will the same thing happen for GLP-1 agonists? The problem is we need both ‘hard-outcome data’ [such as 3-point major adverse cardiovascular events] and more reasonable cost before we see this expanding to an entire population.
“In the future perhaps we could have a biosimilar GLP-1 agonist that would be more affordable than what we pay now, but even before that we need agreement from our reimbursement thought leaders that our society should reimburse these agents.
“My thinking now is the cost-benefit could be favorable, but this is all dependent on what happens to the cost of the drugs over time,” he said.
Additive effect of intensive behavior therapy plus medication
Dr. Wadden explained that intensive behavioral therapy “provides 14 or more counseling sessions in 6 months to modify diet and physical activity, through the patients’ use of behavioral strategies (such as keeping daily food and activity diaries).”
Such programs typically produce mean weight loss of 5%-8% of initial weight; less frequent (e.g., monthly) programs typically produce weight loss of only 1%-3%.
Prior studies suggest that intensive behavioral therapy and medication have additive effects. To investigate this, Dr. Wadden and colleagues randomized 611 adults (81% women) who were a mean age of 46 years and had a mean body mass index of 38 kg/m2.
All participants received 30 intensive behavior therapy sessions provided by a registered dietitian (or other qualified provider), which typically lasted 20-30 minutes and were given weekly for 12 weeks, every other week for the next 12 weeks, and then monthly.
The dietitian gave participants behavioral strategies to help them adhere to diet and physical activity goals.
During the first 8 weeks, participants were provided with a 1,000-1,200 kcal/day meal replacement diet that included liquid shakes, meal bars, and prepared entrees designed to facilitate a large initial weight loss.
They then transitioned to a diet of conventional foods (of their choosing), with a goal of 1,200-1,800 kcal/day based on body weight.
The physical activity goal was 100 minutes/week of walking or other aerobic activity in the first month, building up to 200 minutes/week by month 6.
‘More effective than current FDA-approved weight-loss medications’
At week 68, mean body weight decreased from baseline by 16.0% in the semaglutide group versus 5.7% in the placebo group (P < .0001).
In this trial, where all participants received extensive intensive behavior therapy, more participants had weight loss ≥5%, ≥10%, ≥15%, and ≥20% of their initial weight with semaglutide versus placebo (87% vs. 48%; 75% vs. 27%; 56% vs. 13%; 36% vs. 4%, respectively; all P < .0001).
From baseline to week 68, the proportion of participants with prediabetes decreased from 48% to 7% in the semaglutide group and from 53% to 26% in the placebo group.
Patients who received semaglutide had greater improvements in lipids, too.
Although the weight loss was 10.3% (10.6 kg) greater with semaglutide, Dr. Wadden noted, “additional studies have shown this net benefit to be as great as 11%-12%, which would make semaglutide 2.4 mg more effective than current [FDA-approved] weight-loss medications.”
“Naltrexone-bupropion (Contrave) with lifestyle counseling, for example,” he continued, “produces a loss that is 5 kg greater than lifestyle counseling plus placebo, liraglutide 3.0 mg (Saxenda) a loss 5.3 kg greater than placebo, and phentermine-topiramate (Qsymia) a loss that is 8.8 kg greater than placebo.”
Semaglutide was well tolerated. Gastrointestinal adverse events, the most common type, occurred in 83% of patients in the semaglutide group and 63% of patients in the placebo group.
Nausea, as well as constipation and diarrhea, are common in medications that increase GLP-1 levels, Dr. Wadden noted. Side effects can be managed by slowly increasing the medication dose over 4 months.
Dr. Wadden expects that, if approved, semaglutide 2.4 mg subcutaneous once-weekly will be recommended as an adjunct to a reduced calorie diet and increased physical activity. Additional studies suggest that monthly counseling should be sufficient to obtain similar weight losses as those seen in the current trial, which had more intensive counseling.
As well as being approved as a weekly subcutaneous injectable treatment for type 2 diabetes, semaglutide is also approved as an once-daily oral agent for the same indication (Rybelsus, Novo Nordisk) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
Dr. Wadden serves on scientific advisory boards for Novo Nordisk and WW (formerly Weight Watchers), and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. Dr. Aronne is an investigator in a long-term trial of semaglutide and has served on scientific advisory boards for Novo Nordisk in the past. He also has other industry relationships that are not related to semaglutide.
A version of this article originally appeared on Medscape.com.
‘Disordered eating’ drops after teens undergo bariatric surgery
Kristina M. Decker, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital Medical Center, presented these findings during the virtual ObesityWeek 2020.
Dr. Decker and associates examined rates of disordered eating in more than 200 adolescents (aged 13-18 years) who were severely obese, of whom 141 underwent bariatric surgery and the remainder did not.
At baseline (presurgery), the teens in both groups had rates of disordered eating ranging from 11% to 50%, with higher rates in those who went on to have bariatric surgery.
Six years later, rates of disordered eating were much lower in those who had bariatric surgery.
The data nevertheless “underscore that young adults with persistent severe obesity are at high risk for poor health and well-being,” Dr. Decker said in an interview.
“This means disordered eating behaviors should be closely monitored” in all such patients, both those who undergo surgery and those who don’t, she stressed.
Robust findings because of long follow-up and controls
The findings are not unexpected, based on adult bariatric literature, but are “novel because of the age of the patients,” senior author Margaret H. Zeller, PhD, Cincinnati Children’s Hospital Medical Center and professor at the University of Cincinnati, added.
In a comment comment, psychologist Kajsa Järvholm, PhD, of the Childhood Obesity Unit at Skåne University Hospital, Malmö̈, Sweden, who has published related work, said that this is “a needed study.”
Notably, it had “long-term follow-up and a control group,” and it “confirms that adolescents are in better control of their eating after surgery.”
However, an important additional takeaway for clinicians is that “disordered eating is associated with other mental health problems and self-worth. Clinicians treating obesity must address problems related to eating disorders to improve outcomes and well-being,” she stressed.
How does bariatric surgery impact overeating, binge eating, in teens?
“For teens with severe obesity, metabolic and bariatric surgery is the most effective treatment for improved cardiometabolic functioning, weight loss, and improved quality of life,” Dr. Decker stressed.
However, pre- and postsurgical disordered eating behaviors have been associated with a lower percentage change in body mass index (BMI), although this has not been well studied.
To investigate how disordered eating is affected by bariatric surgery in adolescents with severe obesity, researchers used data from Teen-LABS, which enrolled 242 participants aged 19 years and under who mainly underwent Roux-en-Y gastric bypass (67%) or sleeve gastrectomy (28%) from 2007 to 2012 at five adolescent bariatric surgery centers.
The current analysis examined data from 141 participants in Teen-LABS who underwent bariatric surgery at a mean age of 16.8 years. Mean BMI was 51.5, most were girls (80%), and they had diverse race/ethnicity (66% were White).
Researchers also identified a control group of 83 adolescents of a similar age and gender who had diverse race/ethnicity (54% White) and a mean BMI of 46.9.
At year 6, data were available for 123 young adults in the surgery group (who by then had a mean BMI of 39.7) and 63 young adults in the nonsurgery group (who had a mean BMI of 52.6).
At baseline and year 6, participants replied to questionnaires that identified three eating disorders: continuous eating (eating in an unplanned and repetitious way between meals and snacks), objective overeating (eating a “large” amount of food without loss of control), and objective binge eating (eating a “large” amount of food with loss of control).
At baseline, rates of continuous eating, overeating, and binge eating were higher in the surgical group (50%, 40%, and 30%, respectively) than the nonsurgical group (40%, 22%, and 11%, respectively).
Six years later, when participants were aged 19-24 years, rates of continuous eating, overeating, and binge eating had declined in the surgical group (to 17%, 5%, and 1%, respectively). In the nonsurgical group, only continuous eating and overeating declined (to 24% and 7%, respectively), and binge eating increased slightly (to 13%).
Disordered eating associated with low self-worth, anxiety, and depression
In young adulthood in both groups, disordered eating was associated with lower self-worth. In the surgical group, it was also associated with lower weight-related quality of life, and in the nonsurgical group, it was also associated with anxiety and/or depression.
“The current findings cannot tell us whether disordered eating is a direct result or caused by anxiety, depression, low self-worth, or poor quality of life,” Dr. Decker said.
“These findings do give us insight about what other areas of clinical concern might present together [in] young adults (e.g., disordered eating, low self-esteem).”
Bariatric surgery affects the amount of food people can eat at one time, she noted in reply to a question from the audience. If people eat too much at a time they can experience vomiting, dumping syndrome (where certain food is “dumped” into the small intestine without being digested, causing nausea and vomiting), and plugging (a sense of food becoming stuck).
The home environment and transition to adulthood might impact disordered eating in young adults, she said in reply to another question, but these issues were not examined in this study.
A version of this article originally appeared on Medscape.com.
Kristina M. Decker, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital Medical Center, presented these findings during the virtual ObesityWeek 2020.
Dr. Decker and associates examined rates of disordered eating in more than 200 adolescents (aged 13-18 years) who were severely obese, of whom 141 underwent bariatric surgery and the remainder did not.
At baseline (presurgery), the teens in both groups had rates of disordered eating ranging from 11% to 50%, with higher rates in those who went on to have bariatric surgery.
Six years later, rates of disordered eating were much lower in those who had bariatric surgery.
The data nevertheless “underscore that young adults with persistent severe obesity are at high risk for poor health and well-being,” Dr. Decker said in an interview.
“This means disordered eating behaviors should be closely monitored” in all such patients, both those who undergo surgery and those who don’t, she stressed.
Robust findings because of long follow-up and controls
The findings are not unexpected, based on adult bariatric literature, but are “novel because of the age of the patients,” senior author Margaret H. Zeller, PhD, Cincinnati Children’s Hospital Medical Center and professor at the University of Cincinnati, added.
In a comment comment, psychologist Kajsa Järvholm, PhD, of the Childhood Obesity Unit at Skåne University Hospital, Malmö̈, Sweden, who has published related work, said that this is “a needed study.”
Notably, it had “long-term follow-up and a control group,” and it “confirms that adolescents are in better control of their eating after surgery.”
However, an important additional takeaway for clinicians is that “disordered eating is associated with other mental health problems and self-worth. Clinicians treating obesity must address problems related to eating disorders to improve outcomes and well-being,” she stressed.
How does bariatric surgery impact overeating, binge eating, in teens?
“For teens with severe obesity, metabolic and bariatric surgery is the most effective treatment for improved cardiometabolic functioning, weight loss, and improved quality of life,” Dr. Decker stressed.
However, pre- and postsurgical disordered eating behaviors have been associated with a lower percentage change in body mass index (BMI), although this has not been well studied.
To investigate how disordered eating is affected by bariatric surgery in adolescents with severe obesity, researchers used data from Teen-LABS, which enrolled 242 participants aged 19 years and under who mainly underwent Roux-en-Y gastric bypass (67%) or sleeve gastrectomy (28%) from 2007 to 2012 at five adolescent bariatric surgery centers.
The current analysis examined data from 141 participants in Teen-LABS who underwent bariatric surgery at a mean age of 16.8 years. Mean BMI was 51.5, most were girls (80%), and they had diverse race/ethnicity (66% were White).
Researchers also identified a control group of 83 adolescents of a similar age and gender who had diverse race/ethnicity (54% White) and a mean BMI of 46.9.
At year 6, data were available for 123 young adults in the surgery group (who by then had a mean BMI of 39.7) and 63 young adults in the nonsurgery group (who had a mean BMI of 52.6).
At baseline and year 6, participants replied to questionnaires that identified three eating disorders: continuous eating (eating in an unplanned and repetitious way between meals and snacks), objective overeating (eating a “large” amount of food without loss of control), and objective binge eating (eating a “large” amount of food with loss of control).
At baseline, rates of continuous eating, overeating, and binge eating were higher in the surgical group (50%, 40%, and 30%, respectively) than the nonsurgical group (40%, 22%, and 11%, respectively).
Six years later, when participants were aged 19-24 years, rates of continuous eating, overeating, and binge eating had declined in the surgical group (to 17%, 5%, and 1%, respectively). In the nonsurgical group, only continuous eating and overeating declined (to 24% and 7%, respectively), and binge eating increased slightly (to 13%).
Disordered eating associated with low self-worth, anxiety, and depression
In young adulthood in both groups, disordered eating was associated with lower self-worth. In the surgical group, it was also associated with lower weight-related quality of life, and in the nonsurgical group, it was also associated with anxiety and/or depression.
“The current findings cannot tell us whether disordered eating is a direct result or caused by anxiety, depression, low self-worth, or poor quality of life,” Dr. Decker said.
“These findings do give us insight about what other areas of clinical concern might present together [in] young adults (e.g., disordered eating, low self-esteem).”
Bariatric surgery affects the amount of food people can eat at one time, she noted in reply to a question from the audience. If people eat too much at a time they can experience vomiting, dumping syndrome (where certain food is “dumped” into the small intestine without being digested, causing nausea and vomiting), and plugging (a sense of food becoming stuck).
The home environment and transition to adulthood might impact disordered eating in young adults, she said in reply to another question, but these issues were not examined in this study.
A version of this article originally appeared on Medscape.com.
Kristina M. Decker, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital Medical Center, presented these findings during the virtual ObesityWeek 2020.
Dr. Decker and associates examined rates of disordered eating in more than 200 adolescents (aged 13-18 years) who were severely obese, of whom 141 underwent bariatric surgery and the remainder did not.
At baseline (presurgery), the teens in both groups had rates of disordered eating ranging from 11% to 50%, with higher rates in those who went on to have bariatric surgery.
Six years later, rates of disordered eating were much lower in those who had bariatric surgery.
The data nevertheless “underscore that young adults with persistent severe obesity are at high risk for poor health and well-being,” Dr. Decker said in an interview.
“This means disordered eating behaviors should be closely monitored” in all such patients, both those who undergo surgery and those who don’t, she stressed.
Robust findings because of long follow-up and controls
The findings are not unexpected, based on adult bariatric literature, but are “novel because of the age of the patients,” senior author Margaret H. Zeller, PhD, Cincinnati Children’s Hospital Medical Center and professor at the University of Cincinnati, added.
In a comment comment, psychologist Kajsa Järvholm, PhD, of the Childhood Obesity Unit at Skåne University Hospital, Malmö̈, Sweden, who has published related work, said that this is “a needed study.”
Notably, it had “long-term follow-up and a control group,” and it “confirms that adolescents are in better control of their eating after surgery.”
However, an important additional takeaway for clinicians is that “disordered eating is associated with other mental health problems and self-worth. Clinicians treating obesity must address problems related to eating disorders to improve outcomes and well-being,” she stressed.
How does bariatric surgery impact overeating, binge eating, in teens?
“For teens with severe obesity, metabolic and bariatric surgery is the most effective treatment for improved cardiometabolic functioning, weight loss, and improved quality of life,” Dr. Decker stressed.
However, pre- and postsurgical disordered eating behaviors have been associated with a lower percentage change in body mass index (BMI), although this has not been well studied.
To investigate how disordered eating is affected by bariatric surgery in adolescents with severe obesity, researchers used data from Teen-LABS, which enrolled 242 participants aged 19 years and under who mainly underwent Roux-en-Y gastric bypass (67%) or sleeve gastrectomy (28%) from 2007 to 2012 at five adolescent bariatric surgery centers.
The current analysis examined data from 141 participants in Teen-LABS who underwent bariatric surgery at a mean age of 16.8 years. Mean BMI was 51.5, most were girls (80%), and they had diverse race/ethnicity (66% were White).
Researchers also identified a control group of 83 adolescents of a similar age and gender who had diverse race/ethnicity (54% White) and a mean BMI of 46.9.
At year 6, data were available for 123 young adults in the surgery group (who by then had a mean BMI of 39.7) and 63 young adults in the nonsurgery group (who had a mean BMI of 52.6).
At baseline and year 6, participants replied to questionnaires that identified three eating disorders: continuous eating (eating in an unplanned and repetitious way between meals and snacks), objective overeating (eating a “large” amount of food without loss of control), and objective binge eating (eating a “large” amount of food with loss of control).
At baseline, rates of continuous eating, overeating, and binge eating were higher in the surgical group (50%, 40%, and 30%, respectively) than the nonsurgical group (40%, 22%, and 11%, respectively).
Six years later, when participants were aged 19-24 years, rates of continuous eating, overeating, and binge eating had declined in the surgical group (to 17%, 5%, and 1%, respectively). In the nonsurgical group, only continuous eating and overeating declined (to 24% and 7%, respectively), and binge eating increased slightly (to 13%).
Disordered eating associated with low self-worth, anxiety, and depression
In young adulthood in both groups, disordered eating was associated with lower self-worth. In the surgical group, it was also associated with lower weight-related quality of life, and in the nonsurgical group, it was also associated with anxiety and/or depression.
“The current findings cannot tell us whether disordered eating is a direct result or caused by anxiety, depression, low self-worth, or poor quality of life,” Dr. Decker said.
“These findings do give us insight about what other areas of clinical concern might present together [in] young adults (e.g., disordered eating, low self-esteem).”
Bariatric surgery affects the amount of food people can eat at one time, she noted in reply to a question from the audience. If people eat too much at a time they can experience vomiting, dumping syndrome (where certain food is “dumped” into the small intestine without being digested, causing nausea and vomiting), and plugging (a sense of food becoming stuck).
The home environment and transition to adulthood might impact disordered eating in young adults, she said in reply to another question, but these issues were not examined in this study.
A version of this article originally appeared on Medscape.com.
Obesity biggest risk for COVID-19 pneumonia, after age, male sex
In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.
The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.
Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.
Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.
“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.
And the impact of obesity was most pronounced in women younger than 50 years.
Patients with severe obesity must protect themselves
Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.
Specifically, compared with leaner patients (BMI < 25 kg/m2), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.
“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”
Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”
Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.
The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.
Dr. Pattou agrees, particularly when it comes to severe obesity.
Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.
“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
Untangling BMI from other metabolic risk factors
Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.
Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.
Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.
They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.
They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.
Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).
Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.
Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.
Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.
Each 5-kg/m2 increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.
Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.
The findings were similar across different centers.
“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.
They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”
The study did not receive specific funding. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.
The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.
Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.
Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.
“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.
And the impact of obesity was most pronounced in women younger than 50 years.
Patients with severe obesity must protect themselves
Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.
Specifically, compared with leaner patients (BMI < 25 kg/m2), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.
“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”
Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”
Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.
The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.
Dr. Pattou agrees, particularly when it comes to severe obesity.
Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.
“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
Untangling BMI from other metabolic risk factors
Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.
Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.
Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.
They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.
They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.
Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).
Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.
Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.
Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.
Each 5-kg/m2 increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.
Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.
The findings were similar across different centers.
“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.
They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”
The study did not receive specific funding. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.
The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.
Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.
Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.
“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.
And the impact of obesity was most pronounced in women younger than 50 years.
Patients with severe obesity must protect themselves
Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.
Specifically, compared with leaner patients (BMI < 25 kg/m2), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.
“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”
Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”
Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.
The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.
Dr. Pattou agrees, particularly when it comes to severe obesity.
Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.
“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
Untangling BMI from other metabolic risk factors
Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.
Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.
Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.
They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.
They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.
Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).
Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.
Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.
Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.
Each 5-kg/m2 increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.
Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.
The findings were similar across different centers.
“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.
They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”
The study did not receive specific funding. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.