Obesity

A 50-year-old woman with a history of class 3 obesity, gastroesophageal reflux disease, prediabetes, metabolic dysfunction–associated steatotic liver disease, asthma, and depression returns to our weight management clinic with weight regain 4 years after Roux-en-Y gastric bypass. 

Her initial body weight was 389 lb (176.8 kg; body mass index [BMI], 65), and her nadir weight after surgery was 183 lb (83.2 kg; BMI, 30.5), representing a total weight loss of 53%. During the initial 2 years after surgery, she experienced multiple life stressors and was treated with venlafaxine for mild depression. She regained 25 lb (11.4 kg). Over the next 2 years, she gained another 20 lb (9.1 kg), for a total of 45 lb (20.5 kg) above nadir.

The patient reported increased nighttime consumption of alcohol including vodka, wine, and beer of over 20 drinks per week for the past 2 years. Her laboratory profile showed an elevated fasting glucose level (106 mg/dL, formerly 98 mg/dL), an elevated gamma-glutamyl transferase (GGT) level, and iron deficiency anemia. She admitted to regularly missing doses of postbariatric vitamins and minerals.
 

Ask Patients About Alcohol Use

It’s important to ask patients with significant weight regain after metabolic and bariatric surgery (MBS) about alcohol intake, because patients who have MBS are at an increased risk of developing alcohol use disorder (AUD).

The American Society for Metabolic and Bariatric Surgery recommends screening for alcohol intake both before and after MBS. Underreporting of alcohol consumption is common, but an elevated GGT level or elevated liver enzyme levels can indicate alcohol use. Depression and anxiety exacerbated by life stressors often accompany excessive alcohol intake.

Some antiobesity medications that regulate appetite may also help limit excessive alcohol intake. Naltrexone is used both for the treatment of AUD and for weight management, often in combination with bupropion). In a patient with weight regain and AUD, naltrexone alone would be a reasonable treatment option, although weight loss would probably be modest. The addition of bupropion to naltrexone would probably produce more weight loss; average total body weight loss with bupropion-naltrexone in clinical trials was about 6%. One cautionary note on bupropion: A patient’s seizure history should be elicited, because people with AUD are at increased risk for seizures in the withdrawal stage and bupropion can make those seizures more likely. 

Glucagon-like peptide 1 (GLP-1) receptor agonists (eg, liraglutide and semaglutide) and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide receptor agonists) (eg, tirzepatide) are second-generation antiobesity medications that produce more weight loss than first-generation agents such as bupropion/naltrexone. Of note, prior bariatric surgery was an exclusion criterion in the clinical trials assessing the efficacy of these agents for weight loss. The use of GLP-1 receptor agonists after MBS in people with inadequate weight loss or weight regain has been an area of active research. The BARI-OPTIMISE randomized clinical trial published in 2023 assessed the safety and efficacy of liraglutide 3.0 mg daily in patients with inadequate weight loss after MBS. The mean body weight reduction was 8.82% in the liraglutide group vs 0.54% in the placebo group. 

There is also emerging interest in the potential of GLP-1 receptor agonists in AUD. These medications act on the central nervous system to influence reward pathways. In rodents, studies have shown that GLP-1 receptor agonist administration reduces alcohol intake, although most studies have focused on short-term effects.

A series of experiments assessed the effects of semaglutide on alcohol intake in rodents. The authors found that semaglutide lowered the alcohol-induced release of dopamine and enhanced dopamine metabolism within the nucleus accumbens.

Evidence in humans is still limited, with only one published randomized controlled trial to date. In the 26-week study, weekly exenatide was not superior to placebo in reducing the number of heavy drinking days in patients with AUD who also received cognitive-behavioral therapy. An exploratory analysis in a subgroup of patients with obesity and AUD showed that exenatide reduced alcohol consumption. Of note, exenatide is rarely used in clinical practice because it does not produce substantial weight loss.

Liraglutide was chosen for this patient because of the established efficacy for this agent in patients with a history of MBS. In addition, patients often anecdotally report reduced desire for alcohol while taking a GLP-1 receptor agonist. Although GLP-1 receptor agonists have been shown to reduce alcohol intake in animal studies, their efficacy and safety in humans with AUD are not yet well established.
 

Back to Our Patient: 

Given the patient’s weight regain, an upper gastrointestinal series was performed to rule out gastro-gastric fistula or other anatomic abnormalities. After fistula was ruled out, she was prescribed liraglutide for weight management, which was titrated from 0.6 mg/d to 3 mg/d per the prescribing guidelines. 

With the use of liraglutide over the next year, the patient maintained a stable weight of 200 lb (90.9 kg) and noted that along with reduced appetite, her cravings for alcohol had diminished and she no longer felt the urge to drink alcohol at night. Her fasting glucose and GGT levels normalized. She began to see a nutritionist regularly and was planning to rejoin a bariatric support group.

Dr. Schmitz is an instructor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York. She has disclosed no relevant financial relationships. Dr. Kashyap is a assistant chief of clinical affairs, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell New York Presbyterian, New York. She disclosed ties to GI Dynamics.

A version of this article appeared on Medscape.com.

A 50-year-old woman with a history of class 3 obesity, gastroesophageal reflux disease, prediabetes, metabolic dysfunction–associated steatotic liver disease, asthma, and depression returns to our weight management clinic with weight regain 4 years after Roux-en-Y gastric bypass. 

Her initial body weight was 389 lb (176.8 kg; body mass index [BMI], 65), and her nadir weight after surgery was 183 lb (83.2 kg; BMI, 30.5), representing a total weight loss of 53%. During the initial 2 years after surgery, she experienced multiple life stressors and was treated with venlafaxine for mild depression. She regained 25 lb (11.4 kg). Over the next 2 years, she gained another 20 lb (9.1 kg), for a total of 45 lb (20.5 kg) above nadir.

The patient reported increased nighttime consumption of alcohol including vodka, wine, and beer of over 20 drinks per week for the past 2 years. Her laboratory profile showed an elevated fasting glucose level (106 mg/dL, formerly 98 mg/dL), an elevated gamma-glutamyl transferase (GGT) level, and iron deficiency anemia. She admitted to regularly missing doses of postbariatric vitamins and minerals.
 

Ask Patients About Alcohol Use

It’s important to ask patients with significant weight regain after metabolic and bariatric surgery (MBS) about alcohol intake, because patients who have MBS are at an increased risk of developing alcohol use disorder (AUD).

The American Society for Metabolic and Bariatric Surgery recommends screening for alcohol intake both before and after MBS. Underreporting of alcohol consumption is common, but an elevated GGT level or elevated liver enzyme levels can indicate alcohol use. Depression and anxiety exacerbated by life stressors often accompany excessive alcohol intake.

Some antiobesity medications that regulate appetite may also help limit excessive alcohol intake. Naltrexone is used both for the treatment of AUD and for weight management, often in combination with bupropion). In a patient with weight regain and AUD, naltrexone alone would be a reasonable treatment option, although weight loss would probably be modest. The addition of bupropion to naltrexone would probably produce more weight loss; average total body weight loss with bupropion-naltrexone in clinical trials was about 6%. One cautionary note on bupropion: A patient’s seizure history should be elicited, because people with AUD are at increased risk for seizures in the withdrawal stage and bupropion can make those seizures more likely. 

Glucagon-like peptide 1 (GLP-1) receptor agonists (eg, liraglutide and semaglutide) and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide receptor agonists) (eg, tirzepatide) are second-generation antiobesity medications that produce more weight loss than first-generation agents such as bupropion/naltrexone. Of note, prior bariatric surgery was an exclusion criterion in the clinical trials assessing the efficacy of these agents for weight loss. The use of GLP-1 receptor agonists after MBS in people with inadequate weight loss or weight regain has been an area of active research. The BARI-OPTIMISE randomized clinical trial published in 2023 assessed the safety and efficacy of liraglutide 3.0 mg daily in patients with inadequate weight loss after MBS. The mean body weight reduction was 8.82% in the liraglutide group vs 0.54% in the placebo group. 

There is also emerging interest in the potential of GLP-1 receptor agonists in AUD. These medications act on the central nervous system to influence reward pathways. In rodents, studies have shown that GLP-1 receptor agonist administration reduces alcohol intake, although most studies have focused on short-term effects.

A series of experiments assessed the effects of semaglutide on alcohol intake in rodents. The authors found that semaglutide lowered the alcohol-induced release of dopamine and enhanced dopamine metabolism within the nucleus accumbens.

Evidence in humans is still limited, with only one published randomized controlled trial to date. In the 26-week study, weekly exenatide was not superior to placebo in reducing the number of heavy drinking days in patients with AUD who also received cognitive-behavioral therapy. An exploratory analysis in a subgroup of patients with obesity and AUD showed that exenatide reduced alcohol consumption. Of note, exenatide is rarely used in clinical practice because it does not produce substantial weight loss.

Liraglutide was chosen for this patient because of the established efficacy for this agent in patients with a history of MBS. In addition, patients often anecdotally report reduced desire for alcohol while taking a GLP-1 receptor agonist. Although GLP-1 receptor agonists have been shown to reduce alcohol intake in animal studies, their efficacy and safety in humans with AUD are not yet well established.
 

Back to Our Patient: 

Given the patient’s weight regain, an upper gastrointestinal series was performed to rule out gastro-gastric fistula or other anatomic abnormalities. After fistula was ruled out, she was prescribed liraglutide for weight management, which was titrated from 0.6 mg/d to 3 mg/d per the prescribing guidelines. 

With the use of liraglutide over the next year, the patient maintained a stable weight of 200 lb (90.9 kg) and noted that along with reduced appetite, her cravings for alcohol had diminished and she no longer felt the urge to drink alcohol at night. Her fasting glucose and GGT levels normalized. She began to see a nutritionist regularly and was planning to rejoin a bariatric support group.

Dr. Schmitz is an instructor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York. She has disclosed no relevant financial relationships. Dr. Kashyap is a assistant chief of clinical affairs, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell New York Presbyterian, New York. She disclosed ties to GI Dynamics.

A version of this article appeared on Medscape.com.

A 50-year-old woman with a history of class 3 obesity, gastroesophageal reflux disease, prediabetes, metabolic dysfunction–associated steatotic liver disease, asthma, and depression returns to our weight management clinic with weight regain 4 years after Roux-en-Y gastric bypass. 

Her initial body weight was 389 lb (176.8 kg; body mass index [BMI], 65), and her nadir weight after surgery was 183 lb (83.2 kg; BMI, 30.5), representing a total weight loss of 53%. During the initial 2 years after surgery, she experienced multiple life stressors and was treated with venlafaxine for mild depression. She regained 25 lb (11.4 kg). Over the next 2 years, she gained another 20 lb (9.1 kg), for a total of 45 lb (20.5 kg) above nadir.

The patient reported increased nighttime consumption of alcohol including vodka, wine, and beer of over 20 drinks per week for the past 2 years. Her laboratory profile showed an elevated fasting glucose level (106 mg/dL, formerly 98 mg/dL), an elevated gamma-glutamyl transferase (GGT) level, and iron deficiency anemia. She admitted to regularly missing doses of postbariatric vitamins and minerals.
 

Ask Patients About Alcohol Use

It’s important to ask patients with significant weight regain after metabolic and bariatric surgery (MBS) about alcohol intake, because patients who have MBS are at an increased risk of developing alcohol use disorder (AUD).

The American Society for Metabolic and Bariatric Surgery recommends screening for alcohol intake both before and after MBS. Underreporting of alcohol consumption is common, but an elevated GGT level or elevated liver enzyme levels can indicate alcohol use. Depression and anxiety exacerbated by life stressors often accompany excessive alcohol intake.

Some antiobesity medications that regulate appetite may also help limit excessive alcohol intake. Naltrexone is used both for the treatment of AUD and for weight management, often in combination with bupropion). In a patient with weight regain and AUD, naltrexone alone would be a reasonable treatment option, although weight loss would probably be modest. The addition of bupropion to naltrexone would probably produce more weight loss; average total body weight loss with bupropion-naltrexone in clinical trials was about 6%. One cautionary note on bupropion: A patient’s seizure history should be elicited, because people with AUD are at increased risk for seizures in the withdrawal stage and bupropion can make those seizures more likely. 

Glucagon-like peptide 1 (GLP-1) receptor agonists (eg, liraglutide and semaglutide) and dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide receptor agonists) (eg, tirzepatide) are second-generation antiobesity medications that produce more weight loss than first-generation agents such as bupropion/naltrexone. Of note, prior bariatric surgery was an exclusion criterion in the clinical trials assessing the efficacy of these agents for weight loss. The use of GLP-1 receptor agonists after MBS in people with inadequate weight loss or weight regain has been an area of active research. The BARI-OPTIMISE randomized clinical trial published in 2023 assessed the safety and efficacy of liraglutide 3.0 mg daily in patients with inadequate weight loss after MBS. The mean body weight reduction was 8.82% in the liraglutide group vs 0.54% in the placebo group. 

There is also emerging interest in the potential of GLP-1 receptor agonists in AUD. These medications act on the central nervous system to influence reward pathways. In rodents, studies have shown that GLP-1 receptor agonist administration reduces alcohol intake, although most studies have focused on short-term effects.

A series of experiments assessed the effects of semaglutide on alcohol intake in rodents. The authors found that semaglutide lowered the alcohol-induced release of dopamine and enhanced dopamine metabolism within the nucleus accumbens.

Evidence in humans is still limited, with only one published randomized controlled trial to date. In the 26-week study, weekly exenatide was not superior to placebo in reducing the number of heavy drinking days in patients with AUD who also received cognitive-behavioral therapy. An exploratory analysis in a subgroup of patients with obesity and AUD showed that exenatide reduced alcohol consumption. Of note, exenatide is rarely used in clinical practice because it does not produce substantial weight loss.

Liraglutide was chosen for this patient because of the established efficacy for this agent in patients with a history of MBS. In addition, patients often anecdotally report reduced desire for alcohol while taking a GLP-1 receptor agonist. Although GLP-1 receptor agonists have been shown to reduce alcohol intake in animal studies, their efficacy and safety in humans with AUD are not yet well established.
 

Back to Our Patient: 

Given the patient’s weight regain, an upper gastrointestinal series was performed to rule out gastro-gastric fistula or other anatomic abnormalities. After fistula was ruled out, she was prescribed liraglutide for weight management, which was titrated from 0.6 mg/d to 3 mg/d per the prescribing guidelines. 

With the use of liraglutide over the next year, the patient maintained a stable weight of 200 lb (90.9 kg) and noted that along with reduced appetite, her cravings for alcohol had diminished and she no longer felt the urge to drink alcohol at night. Her fasting glucose and GGT levels normalized. She began to see a nutritionist regularly and was planning to rejoin a bariatric support group.

Dr. Schmitz is an instructor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York. She has disclosed no relevant financial relationships. Dr. Kashyap is a assistant chief of clinical affairs, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell New York Presbyterian, New York. She disclosed ties to GI Dynamics.

A version of this article appeared on Medscape.com.

Claudia* was a charming 27-year-old newlywed. She and her husband wanted to start a family — with one small catch. She had recently gained 30 pounds. During COVID, she and her husband spent 18 months camped out in her parents’ guest room in upstate New York and had eaten their emotions with abandon. They ate when they were happy and ate more when they were sad. They ate when they felt isolated and again when they felt anxious. It didn’t help that her mother was a Culinary Institute–trained amateur chef. They both worked from home and logged long hours on Zoom calls. Because there was no home gym, they replaced their usual fitness club workouts in the city with leisurely strolls around the local lake. When I met her, Claudia categorically refused to entertain the notion of pregnancy until she reached her pre-COVID weight.

At the time, this all seemed quite reasonable to me. We outlined a plan including semaglutide (Wegovy) until she reached her target weight and then a minimum of 2 months off Wegovy prior to conception. We also lined up sessions with a dietitian and trainer and renewed her birth control pill. There was one detail I failed to mention to her: Birth control pills are less effective while on incretin hormones like semaglutide. The reason for my omission is that the medical community at large wasn’t yet aware of this issue. 

About 12 weeks into treatment, Claudia had lost 20 of the 30 pounds. She had canceled several appointments with the trainer and dietitian due to work conflicts. She messaged me over the weekend in a panic. Her period was late, and her pregnancy test was positive.

She had three pressing questions for me:

Q: How had this happened while she had taken the birth control pills faithfully?

A: I answered that the scientific reasons for the decrease in efficacy of birth control pills while on semaglutide medications are threefold: 

• Weight loss can improve menstrual cycle irregularities and improve fertility. In fact, I have been using semaglutide-like medications to treat polycystic ovary syndrome for decades, well before these medications became mainstream.
• The delayed gastric emptying inherent to incretins leads to decreased absorption of birth control pills.
• Finally, while this did not apply to Claudia, no medicine is particularly efficacious if vomited up shortly after taking. Wegovy is known to cause nausea and vomiting in a sizable percentage of patients.

Q: Would she have a healthy pregnancy given the lingering effects of Wegovy?

A: The short answer is: most likely yes. A review of the package insert revealed something fascinating. It was not strictly contraindicated. It advised doctors to weigh the risks and benefits of the medication during pregnancy. Animal studies have shown that semaglutide increases the risk for fetal death, birth defects, and growth issues, but this is probably due to restrictive eating patterns rather than a direct effect of the medication. A recent study of health records of more than 50,000 women with diabetes who had been inadvertently taking these medications in early pregnancy showed no increase in birth defects when compared with women who took insulin.

Q: What would happen to her weight loss efforts?

A: To address her third concern, I tried to offset the risk for rebound weight gain by stopping Wegovy and giving her metformin in the second and third trimesters. Considered a safe medication in pregnancy, metformin is thought to support weight loss, but it proved to be ineffective against the rebound weight gain from stopping Wegovy. Claudia had not resumed regular exercise and quickly fell into the age-old eating-for-two trap. She gained nearly 50 pounds over the course of her pregnancy. 

After a short and unfulfilling attempt at nursing, Claudia restarted Wegovy, this time in conjunction with a Mediterranean meal plan and regular sessions at a fitness club. After losing the pregnancy weight, she has been able to successfully maintain her ideal body weight for the past year, and her baby is perfectly healthy and beautiful. 

*Patient’s name changed. 

A version of this article appeared on Medscape.com.

Claudia* was a charming 27-year-old newlywed. She and her husband wanted to start a family — with one small catch. She had recently gained 30 pounds. During COVID, she and her husband spent 18 months camped out in her parents’ guest room in upstate New York and had eaten their emotions with abandon. They ate when they were happy and ate more when they were sad. They ate when they felt isolated and again when they felt anxious. It didn’t help that her mother was a Culinary Institute–trained amateur chef. They both worked from home and logged long hours on Zoom calls. Because there was no home gym, they replaced their usual fitness club workouts in the city with leisurely strolls around the local lake. When I met her, Claudia categorically refused to entertain the notion of pregnancy until she reached her pre-COVID weight.

At the time, this all seemed quite reasonable to me. We outlined a plan including semaglutide (Wegovy) until she reached her target weight and then a minimum of 2 months off Wegovy prior to conception. We also lined up sessions with a dietitian and trainer and renewed her birth control pill. There was one detail I failed to mention to her: Birth control pills are less effective while on incretin hormones like semaglutide. The reason for my omission is that the medical community at large wasn’t yet aware of this issue. 

About 12 weeks into treatment, Claudia had lost 20 of the 30 pounds. She had canceled several appointments with the trainer and dietitian due to work conflicts. She messaged me over the weekend in a panic. Her period was late, and her pregnancy test was positive.

She had three pressing questions for me:

Q: How had this happened while she had taken the birth control pills faithfully?

A: I answered that the scientific reasons for the decrease in efficacy of birth control pills while on semaglutide medications are threefold: 

• Weight loss can improve menstrual cycle irregularities and improve fertility. In fact, I have been using semaglutide-like medications to treat polycystic ovary syndrome for decades, well before these medications became mainstream.
• The delayed gastric emptying inherent to incretins leads to decreased absorption of birth control pills.
• Finally, while this did not apply to Claudia, no medicine is particularly efficacious if vomited up shortly after taking. Wegovy is known to cause nausea and vomiting in a sizable percentage of patients.

Q: Would she have a healthy pregnancy given the lingering effects of Wegovy?

A: The short answer is: most likely yes. A review of the package insert revealed something fascinating. It was not strictly contraindicated. It advised doctors to weigh the risks and benefits of the medication during pregnancy. Animal studies have shown that semaglutide increases the risk for fetal death, birth defects, and growth issues, but this is probably due to restrictive eating patterns rather than a direct effect of the medication. A recent study of health records of more than 50,000 women with diabetes who had been inadvertently taking these medications in early pregnancy showed no increase in birth defects when compared with women who took insulin.

Q: What would happen to her weight loss efforts?

A: To address her third concern, I tried to offset the risk for rebound weight gain by stopping Wegovy and giving her metformin in the second and third trimesters. Considered a safe medication in pregnancy, metformin is thought to support weight loss, but it proved to be ineffective against the rebound weight gain from stopping Wegovy. Claudia had not resumed regular exercise and quickly fell into the age-old eating-for-two trap. She gained nearly 50 pounds over the course of her pregnancy. 

After a short and unfulfilling attempt at nursing, Claudia restarted Wegovy, this time in conjunction with a Mediterranean meal plan and regular sessions at a fitness club. After losing the pregnancy weight, she has been able to successfully maintain her ideal body weight for the past year, and her baby is perfectly healthy and beautiful. 

*Patient’s name changed. 

A version of this article appeared on Medscape.com.

Claudia* was a charming 27-year-old newlywed. She and her husband wanted to start a family — with one small catch. She had recently gained 30 pounds. During COVID, she and her husband spent 18 months camped out in her parents’ guest room in upstate New York and had eaten their emotions with abandon. They ate when they were happy and ate more when they were sad. They ate when they felt isolated and again when they felt anxious. It didn’t help that her mother was a Culinary Institute–trained amateur chef. They both worked from home and logged long hours on Zoom calls. Because there was no home gym, they replaced their usual fitness club workouts in the city with leisurely strolls around the local lake. When I met her, Claudia categorically refused to entertain the notion of pregnancy until she reached her pre-COVID weight.

At the time, this all seemed quite reasonable to me. We outlined a plan including semaglutide (Wegovy) until she reached her target weight and then a minimum of 2 months off Wegovy prior to conception. We also lined up sessions with a dietitian and trainer and renewed her birth control pill. There was one detail I failed to mention to her: Birth control pills are less effective while on incretin hormones like semaglutide. The reason for my omission is that the medical community at large wasn’t yet aware of this issue. 

About 12 weeks into treatment, Claudia had lost 20 of the 30 pounds. She had canceled several appointments with the trainer and dietitian due to work conflicts. She messaged me over the weekend in a panic. Her period was late, and her pregnancy test was positive.

She had three pressing questions for me:

Q: How had this happened while she had taken the birth control pills faithfully?

A: I answered that the scientific reasons for the decrease in efficacy of birth control pills while on semaglutide medications are threefold: 

• Weight loss can improve menstrual cycle irregularities and improve fertility. In fact, I have been using semaglutide-like medications to treat polycystic ovary syndrome for decades, well before these medications became mainstream.
• The delayed gastric emptying inherent to incretins leads to decreased absorption of birth control pills.
• Finally, while this did not apply to Claudia, no medicine is particularly efficacious if vomited up shortly after taking. Wegovy is known to cause nausea and vomiting in a sizable percentage of patients.

Q: Would she have a healthy pregnancy given the lingering effects of Wegovy?

A: The short answer is: most likely yes. A review of the package insert revealed something fascinating. It was not strictly contraindicated. It advised doctors to weigh the risks and benefits of the medication during pregnancy. Animal studies have shown that semaglutide increases the risk for fetal death, birth defects, and growth issues, but this is probably due to restrictive eating patterns rather than a direct effect of the medication. A recent study of health records of more than 50,000 women with diabetes who had been inadvertently taking these medications in early pregnancy showed no increase in birth defects when compared with women who took insulin.

Q: What would happen to her weight loss efforts?

A: To address her third concern, I tried to offset the risk for rebound weight gain by stopping Wegovy and giving her metformin in the second and third trimesters. Considered a safe medication in pregnancy, metformin is thought to support weight loss, but it proved to be ineffective against the rebound weight gain from stopping Wegovy. Claudia had not resumed regular exercise and quickly fell into the age-old eating-for-two trap. She gained nearly 50 pounds over the course of her pregnancy. 

After a short and unfulfilling attempt at nursing, Claudia restarted Wegovy, this time in conjunction with a Mediterranean meal plan and regular sessions at a fitness club. After losing the pregnancy weight, she has been able to successfully maintain her ideal body weight for the past year, and her baby is perfectly healthy and beautiful. 

*Patient’s name changed. 

A version of this article appeared on Medscape.com.

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

VIENNA — With the glucagon-like peptide (GLP) 1 receptor agonist semaglutide (Wegovy) recently shown to significantly induce weight loss in people with osteoarthritis (OA) and obesity in the STEP-9 trial, could drugs traditionally used to treat type 2 diabetes be the next big thing for OA management?

“Hormone-based weight loss drugs are a game changer” for obesity management, Sébastien Czernichow, MD, PhD, said during a plenary session at the OARSI 2024 World Congress.

Sara Freeman/Medscape Medical News

Drugs such as semaglutide may also have a cardioprotective effect, reducing the risk for major adverse cardiovascular events by as much as 20% vs placebo, added Dr. Czernichow, professor of nutrition at Paris Cité University and head of the Department of Nutrition at the George Pompidou European Hospital in Paris, France.

“You have to keep in mind that the short-term side effects are mainly gastrointestinal and [are] manageable. The mid-term side effects are an increased gallbladder [disease] risk, and the long-term benefits and risks are not really well known yet,” Dr. Czernichow said. With regard to that, the effects of these drugs on lean body mass, bone health, and nutritional deficiencies need to be further evaluated and monitored.
 

Weight Loss Benefits

Weight loss is one of the cornerstones of OA management, and in addition to the weight loss seen with the GLP-1 receptor agonists, there have also been changes in body composition, Dr. Czernichow said.

In SURMOUNT-1, for example, the dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide (Zepbound) was shown to significantly reduce total fat mass with a smaller decrease in total lean mass in a subanalysis.

It has been argued that effects on body composition need to be considered when evaluating new weight loss drugs, and that focusing only on the degree of weight reduction is “encouraging inaccurate measures of medication efficacy for both patients and clinicians,” Dr. Czernichow said, citing a viewpoint published in JAMA Internal Medicine.

“The real question is: Are we able to fund these drugs for everyone? Or will only the richest patients be allocated to these drugs?” Dr. Czernichow said.
 

Weight Rebound

Tonia Vincent, MBBS, PhD, professor of musculoskeletal biology and an honorary rheumatologist at The Kennedy Institute of Rheumatology at University of Oxford in England, was concerned about rebound weight gain.

“We hear a lot about this, that people stopping drugs actually get worse weight gain than before they started, and that’s a concern about a drug that is going to have a huge pressure for supply,” Dr. Vincent said following Dr. Czernichow’s presentation.

Another delegate said that calling GLP-1 receptor agonists a “game changer” for weight loss in OA was premature because long-term results are needed.

“You mentioned that the double-digit weight loss is getting very close to the results from bariatric surgery, but bariatric surgery you do once, and for these drugs, to maintain the weight loss, you need to take them continuously,” she said.
 

Weight Loss Affects Bone

Yet another delegate cautioned on the potential effects of significant weight loss on bone and cartilage. There is evidence, he said, that weight loss of 5-10 kg can significantly affect bone turnover, increasing bone resorption and thus putting patients at a risk of becoming osteopenic. “Are we looking at a new population of osteoporosis patients who may then also be at risk for fractures?” he asked.

Separately at OARSI 2024, Anne C. Bay-Jensen, PhD, chief technology officer at Nordic Bioscience in Herlev, Denmark, and colleagues reported data showing that weight loss was associated with an increase in bone and cartilage degradation.

Although Dr. Bay-Jensen and colleagues found that losing weight was associated with improved patient outcomes, there was a 1.58-fold increase in the bone resorption marker CTX-I in people who had lost weight vs a 1.37-fold gain in those whose weight remained stable and 1.11-fold increase in those who gained weight.

Moreover, there was a 1.15-fold increase in the cartilage degradation marker C2M in the weight loss group and 0.84-fold decrease in the interstitial matrix degradation marker C3M.
 

GLP-1 and Bone Effects

Another question is whether GLP-1 receptor agonists might be having direct effects on the bone that may be beneficial in OA. They might, postdoctoral researcher Eda Çiftci, PhD, of AO Research Institute Davos in Switzerland, and collaborators, said during the poster sessions at OARSI 2024.

Dr. Çiftci and researchers reported the findings of an in vitro study that looked at whether liraglutide might have anti-inflammatory and anabolic effects on a human chondrocytes model that had been treated with interleukin (IL)-1-beta to “mimic an inflammatory OA condition.”

The release of the proinflammatory cytokines IL-6 and IL-8 was reduced by treatment with liraglutide when compared with control chondrocytes. Furthermore, the expression of the proteoglycan aggrecan — important for articular cartilage function — also was preserved.

These results suggest that liraglutide does indeed have anabolic and anti-inflammatory effects, Dr. Çiftci and fellow researchers concluded.
 

New Role for Dipeptidyl Transferase Inhibitors?

Researchers are also looking at the potential role for other diabetes medications in OA management, including the dipeptidyl peptidase (DPP) 4 inhibitors.

Although these drugs are considered “weight neutral,” in vitro studies have suggested that the DPP4 enzyme may have a role to play in chondrocyte survival and inflammation, Yu-Hsiu Chen, MD, of the Tri-Service General Hospital and the National Defense Medical Center in Taipei, Taiwan, told this news organization. The DPP4 enzyme inactivates GLP-1, so there is rationale there.

“Last year, we published a paper where we found the concentration of DPP4 in the synovial fluid was correlated with radiographic change in knee OA,” Dr. Chen said. This time, “we’re trying to see if a DPP4 inhibitor can be used as a treatment.”

For their analysis, they used data on people newly diagnosed with type 2 diabetes who were and were not using DPP4 inhibitors obtained from Taiwan’s National Health Insurance Research Database. This database contains information on 99% of the Taiwanese population, Dr. Chen said.

Matching 165,333 DPP4 inhibitor users with an equal number of nonusers showed that there was a significant 58% risk reduction for developing OA with DPP4 inhibitor use (hazard ratio, 0.42; 95% CI, 0.41-0.44).

DPP4 inhibitor use was also associated with a 58% risk lower risk for total knee replacement (TKR) and a 62% lower risk for total hip replacement.

Dr. Chen and colleagues concluded: “These results strongly indicate that DPP4 inhibitors could be considered as a viable treatment approach for individuals with type 2 [diabetes mellitus] who are at risk for developing OA or [who] already have OA.”
 

Could Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors Be Beneficial?

So, what about SGLT2 inhibitors? Do they also have a potential role to play in managing people with OA, regardless of whether there is diabetes present? Perhaps, and their effect may be even greater than what’s been observed for GLP-1 receptor agonists, as data presented by epidemiologist S. Reza Jafarzadeh, DVM, PhD, suggested.

“While GLP-1 receptor agonist drugs have been reported to reduce OA risk, largely attributed to their weight loss effect, SGLT2 inhibitors may provide a greater protective effect on OA outcomes,” said Dr. Jafarzadeh, assistant professor at Boston University.

Sara Freeman/Medscape Medical News

The congress was sponsored by the Osteoarthritis Research Society International.

Dr. Czernichow disclosed ties with BariaTek Medical, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Janssen, Jellynov, Lilly, Novo Nordisk, Novartis, and ViiV Healthcare. Dr. Vincent had no relevant disclosures. Dr. Bay-Jensen is the chief technology officer and director of immunoscience at Nordic Bioscience, which funded the work in the poster she presented at OARSI 2024. The work presented by Dr. Çiftci and colleagues was funded by the Eurostars-2 joint program with co-funding from the European Horizon 2020 research and innovation program. Dr. Çiftci had no personal disclosures to report. Dr. Chen’s work was supported by the government of Taiwan, and she had no financial conflicts of interest to disclose. Dr. Jafarzadeh had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com .

DENVER — In addition to the established gastrointestinal side effects common with the highly effective anti-obesity drugs, there is growing discussion around their potential to contribute to the loss of lean mass, necessary to keep the metabolic engine running full-steam.

And although measures should be recommended to prevent those effects, experts also want to remind clinicians that the loss of lean mass is indeed expected with most weight loss interventions — when they’re successful.

“The bottom line is if you’re successful with weight loss, it’s a normal process that you’re going to lose some lean mass,” Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center in Boston, said during a presentation on the issue at Obesity Medicine 2024.

“It’s what we would expect to see if you successfully lost weight with bariatric surgery or with an intense lifestyle intervention,” said Dr. Fitch, past president of the Obesity Medicine Association.

“The difference is, there haven’t been nearly as many people being successful with weight loss with those other interventions,” she noted. “But with the popularity of the glucagon-like peptide 1 (GLP-1) medications, people are hearing this for the first time and saying, ‘Oh my gosh, 30% of the weight loss is muscle mass — that’s horrible.’ “

An underlying goal in the treatment of obesity is the reduction of fat mass, and significant fat mass reduction can provide benefits exceeding the drawbacks resulting from lean mass loss, which have been reported in clinical trials of the GLP-1s semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide to range from about 25% to 40%, respectively, of weight loss.

“Excess adiposity is what makes us sick — not our weight,” Dr. Fitch underscored. “The amount of fat that people are losing [with anti-obesity medications] is far more beneficial than maybe the potential that they’ve lost a little bit of lean mass,” she said.

She cited research suggesting that significant weight loss from bariatric surgery is linked to increases in life expectancy, cardiovascular risk reduction, cancer risk reduction, and a wide array of other positive effects — despite the loss of lean mass that occurs with the weight loss.

Opportunity for Awareness

The increased attention on issues of body composition accompanying weight loss importantly provides clinicians the chance to underscore to patients the importance of offsetting the loss of lean mass through strength training, nutritional choices, and other measures.

However, patients should be prepared that achieving these goals can be more challenging than expected, said Dr. Fitch.

“It can be very hard to be in an energy deficit (due to a weight loss regimen) and gain muscle mass,” she said. “When athletes are trying to gain muscle mass, they’re increasing their intake to do so. It doesn’t come naturally in today’s world.”

Nevertheless, patients can be reassured that the losses can be reversed with some effort, Dr. Fitch noted.

She cautioned that for those who succeed in building or rebuilding lean mass, the evidence may be reflected on the scale, with numbers going up, not down — something they may not wish to see.

“Patients tend to freak out when they see the scale going up after losing all of that weight, but you can reassure them that it’s okay — this is healthier weight gain.”

Special Considerations in Older Patients

Efforts at staving off lean mass loss are particularly important in older patients, who are already most vulnerable to experiencing it naturally with age, even if not on a weight loss regimen.

But Dr. Fitch offered that age does not necessarily have to be a barrier in tackling those effects.

She described two cases of treating patients in their mid-70s, a male and female, with GLP-1s for obesity. Not only were they able to achieve substantial reductions in body mass index over nearly a year on treatment, but they were also able to avoid skeletal muscle mass loss during a period when it would have likely naturally occurred.

She noted the need to augment strength training with protein intake to help build muscle, citing recommendations including consumption of 1.4-2.0 g of protein per kg of body weight for building muscle and maintaining muscle mass.

Importantly, “make sure patients aren’t too appetite suppressed so they can keep up with their nutrition,” Dr. Fitch said.

A key condition to watch for in these patients is sarcopenia. Definitions of sarcopenia vary, but it is distinguished by low skeletal muscle mass and either low muscle strength — measured, for instance, with hand grip — or low muscle performance, such as reduced walking speed or muscle power, Dr. Fitch said.

In such cases, patients may need special considerations, including avoiding significant caloric deficits and whether the risks of medication outweigh the benefits.

‘Super-Responders’ and Other Lean Mass Loss Scenarios

Further addressing the issues of body composition and weight loss at the meeting, Robert F. Kushner, MD, professor of medicine and medicine education at Northwestern University in Chicago, noted that one area of concern regarding lean mass loss is “super-responders” — patients who have exceptionally high weight loss on GLP-1s.

“We are concerned about individuals who experience very high weight loss responses to medication, [specifically] 25% or more weight loss, as well as individuals at higher risk of losing lean body mass [muscle mass], specifically people in their 50s, 60s, and 70s,” Dr. Kushner told this news organization.

“Lifestyle counseling, particularly regarding safety and body composition, is recommended in these patients,” he said, adding that in managing these patients, “the approach is to use close patient monitoring, dose reduction if needed, and emphasizing a high-protein diet accompanied by aerobic and resistance physical activity.”

Potentially dramatic lean mass loss can occur in obesity whether or not patients are on obesity medications. As evidence of this, Dr. Kushner cited a subanalysis of the Look AHEAD trial of 1019 overweight or obese patients who had a mean age of 58 years at baseline. Patients were randomized to either a physical activity and reduced calorie intervention group or simply education.

Although the results showed that fat losses in the intervention group were generally regained over 8 years, a striking, steady decline was observed in lean mass in both the intervention and control groups, including men and women.

Dr. Fitch disclosed ties to Eli Lilly, Novo Nordisk, Currax, Vivus, SideKick Health, Jenny Craig, Carmot, and Seca. Dr. Kushner is on the advisory boards of Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — In addition to the established gastrointestinal side effects common with the highly effective anti-obesity drugs, there is growing discussion around their potential to contribute to the loss of lean mass, necessary to keep the metabolic engine running full-steam.

And although measures should be recommended to prevent those effects, experts also want to remind clinicians that the loss of lean mass is indeed expected with most weight loss interventions — when they’re successful.

“The bottom line is if you’re successful with weight loss, it’s a normal process that you’re going to lose some lean mass,” Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center in Boston, said during a presentation on the issue at Obesity Medicine 2024.

“It’s what we would expect to see if you successfully lost weight with bariatric surgery or with an intense lifestyle intervention,” said Dr. Fitch, past president of the Obesity Medicine Association.

“The difference is, there haven’t been nearly as many people being successful with weight loss with those other interventions,” she noted. “But with the popularity of the glucagon-like peptide 1 (GLP-1) medications, people are hearing this for the first time and saying, ‘Oh my gosh, 30% of the weight loss is muscle mass — that’s horrible.’ “

An underlying goal in the treatment of obesity is the reduction of fat mass, and significant fat mass reduction can provide benefits exceeding the drawbacks resulting from lean mass loss, which have been reported in clinical trials of the GLP-1s semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide to range from about 25% to 40%, respectively, of weight loss.

“Excess adiposity is what makes us sick — not our weight,” Dr. Fitch underscored. “The amount of fat that people are losing [with anti-obesity medications] is far more beneficial than maybe the potential that they’ve lost a little bit of lean mass,” she said.

She cited research suggesting that significant weight loss from bariatric surgery is linked to increases in life expectancy, cardiovascular risk reduction, cancer risk reduction, and a wide array of other positive effects — despite the loss of lean mass that occurs with the weight loss.

Opportunity for Awareness

The increased attention on issues of body composition accompanying weight loss importantly provides clinicians the chance to underscore to patients the importance of offsetting the loss of lean mass through strength training, nutritional choices, and other measures.

However, patients should be prepared that achieving these goals can be more challenging than expected, said Dr. Fitch.

“It can be very hard to be in an energy deficit (due to a weight loss regimen) and gain muscle mass,” she said. “When athletes are trying to gain muscle mass, they’re increasing their intake to do so. It doesn’t come naturally in today’s world.”

Nevertheless, patients can be reassured that the losses can be reversed with some effort, Dr. Fitch noted.

She cautioned that for those who succeed in building or rebuilding lean mass, the evidence may be reflected on the scale, with numbers going up, not down — something they may not wish to see.

“Patients tend to freak out when they see the scale going up after losing all of that weight, but you can reassure them that it’s okay — this is healthier weight gain.”

Special Considerations in Older Patients

Efforts at staving off lean mass loss are particularly important in older patients, who are already most vulnerable to experiencing it naturally with age, even if not on a weight loss regimen.

But Dr. Fitch offered that age does not necessarily have to be a barrier in tackling those effects.

She described two cases of treating patients in their mid-70s, a male and female, with GLP-1s for obesity. Not only were they able to achieve substantial reductions in body mass index over nearly a year on treatment, but they were also able to avoid skeletal muscle mass loss during a period when it would have likely naturally occurred.

She noted the need to augment strength training with protein intake to help build muscle, citing recommendations including consumption of 1.4-2.0 g of protein per kg of body weight for building muscle and maintaining muscle mass.

Importantly, “make sure patients aren’t too appetite suppressed so they can keep up with their nutrition,” Dr. Fitch said.

A key condition to watch for in these patients is sarcopenia. Definitions of sarcopenia vary, but it is distinguished by low skeletal muscle mass and either low muscle strength — measured, for instance, with hand grip — or low muscle performance, such as reduced walking speed or muscle power, Dr. Fitch said.

In such cases, patients may need special considerations, including avoiding significant caloric deficits and whether the risks of medication outweigh the benefits.

‘Super-Responders’ and Other Lean Mass Loss Scenarios

Further addressing the issues of body composition and weight loss at the meeting, Robert F. Kushner, MD, professor of medicine and medicine education at Northwestern University in Chicago, noted that one area of concern regarding lean mass loss is “super-responders” — patients who have exceptionally high weight loss on GLP-1s.

“We are concerned about individuals who experience very high weight loss responses to medication, [specifically] 25% or more weight loss, as well as individuals at higher risk of losing lean body mass [muscle mass], specifically people in their 50s, 60s, and 70s,” Dr. Kushner told this news organization.

“Lifestyle counseling, particularly regarding safety and body composition, is recommended in these patients,” he said, adding that in managing these patients, “the approach is to use close patient monitoring, dose reduction if needed, and emphasizing a high-protein diet accompanied by aerobic and resistance physical activity.”

Potentially dramatic lean mass loss can occur in obesity whether or not patients are on obesity medications. As evidence of this, Dr. Kushner cited a subanalysis of the Look AHEAD trial of 1019 overweight or obese patients who had a mean age of 58 years at baseline. Patients were randomized to either a physical activity and reduced calorie intervention group or simply education.

Although the results showed that fat losses in the intervention group were generally regained over 8 years, a striking, steady decline was observed in lean mass in both the intervention and control groups, including men and women.

Dr. Fitch disclosed ties to Eli Lilly, Novo Nordisk, Currax, Vivus, SideKick Health, Jenny Craig, Carmot, and Seca. Dr. Kushner is on the advisory boards of Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — In addition to the established gastrointestinal side effects common with the highly effective anti-obesity drugs, there is growing discussion around their potential to contribute to the loss of lean mass, necessary to keep the metabolic engine running full-steam.

And although measures should be recommended to prevent those effects, experts also want to remind clinicians that the loss of lean mass is indeed expected with most weight loss interventions — when they’re successful.

“The bottom line is if you’re successful with weight loss, it’s a normal process that you’re going to lose some lean mass,” Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center in Boston, said during a presentation on the issue at Obesity Medicine 2024.

“It’s what we would expect to see if you successfully lost weight with bariatric surgery or with an intense lifestyle intervention,” said Dr. Fitch, past president of the Obesity Medicine Association.

“The difference is, there haven’t been nearly as many people being successful with weight loss with those other interventions,” she noted. “But with the popularity of the glucagon-like peptide 1 (GLP-1) medications, people are hearing this for the first time and saying, ‘Oh my gosh, 30% of the weight loss is muscle mass — that’s horrible.’ “

An underlying goal in the treatment of obesity is the reduction of fat mass, and significant fat mass reduction can provide benefits exceeding the drawbacks resulting from lean mass loss, which have been reported in clinical trials of the GLP-1s semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide to range from about 25% to 40%, respectively, of weight loss.

“Excess adiposity is what makes us sick — not our weight,” Dr. Fitch underscored. “The amount of fat that people are losing [with anti-obesity medications] is far more beneficial than maybe the potential that they’ve lost a little bit of lean mass,” she said.

She cited research suggesting that significant weight loss from bariatric surgery is linked to increases in life expectancy, cardiovascular risk reduction, cancer risk reduction, and a wide array of other positive effects — despite the loss of lean mass that occurs with the weight loss.

Opportunity for Awareness

The increased attention on issues of body composition accompanying weight loss importantly provides clinicians the chance to underscore to patients the importance of offsetting the loss of lean mass through strength training, nutritional choices, and other measures.

However, patients should be prepared that achieving these goals can be more challenging than expected, said Dr. Fitch.

“It can be very hard to be in an energy deficit (due to a weight loss regimen) and gain muscle mass,” she said. “When athletes are trying to gain muscle mass, they’re increasing their intake to do so. It doesn’t come naturally in today’s world.”

Nevertheless, patients can be reassured that the losses can be reversed with some effort, Dr. Fitch noted.

She cautioned that for those who succeed in building or rebuilding lean mass, the evidence may be reflected on the scale, with numbers going up, not down — something they may not wish to see.

“Patients tend to freak out when they see the scale going up after losing all of that weight, but you can reassure them that it’s okay — this is healthier weight gain.”

Special Considerations in Older Patients

Efforts at staving off lean mass loss are particularly important in older patients, who are already most vulnerable to experiencing it naturally with age, even if not on a weight loss regimen.

But Dr. Fitch offered that age does not necessarily have to be a barrier in tackling those effects.

She described two cases of treating patients in their mid-70s, a male and female, with GLP-1s for obesity. Not only were they able to achieve substantial reductions in body mass index over nearly a year on treatment, but they were also able to avoid skeletal muscle mass loss during a period when it would have likely naturally occurred.

She noted the need to augment strength training with protein intake to help build muscle, citing recommendations including consumption of 1.4-2.0 g of protein per kg of body weight for building muscle and maintaining muscle mass.

Importantly, “make sure patients aren’t too appetite suppressed so they can keep up with their nutrition,” Dr. Fitch said.

A key condition to watch for in these patients is sarcopenia. Definitions of sarcopenia vary, but it is distinguished by low skeletal muscle mass and either low muscle strength — measured, for instance, with hand grip — or low muscle performance, such as reduced walking speed or muscle power, Dr. Fitch said.

In such cases, patients may need special considerations, including avoiding significant caloric deficits and whether the risks of medication outweigh the benefits.

‘Super-Responders’ and Other Lean Mass Loss Scenarios

Further addressing the issues of body composition and weight loss at the meeting, Robert F. Kushner, MD, professor of medicine and medicine education at Northwestern University in Chicago, noted that one area of concern regarding lean mass loss is “super-responders” — patients who have exceptionally high weight loss on GLP-1s.

“We are concerned about individuals who experience very high weight loss responses to medication, [specifically] 25% or more weight loss, as well as individuals at higher risk of losing lean body mass [muscle mass], specifically people in their 50s, 60s, and 70s,” Dr. Kushner told this news organization.

“Lifestyle counseling, particularly regarding safety and body composition, is recommended in these patients,” he said, adding that in managing these patients, “the approach is to use close patient monitoring, dose reduction if needed, and emphasizing a high-protein diet accompanied by aerobic and resistance physical activity.”

Potentially dramatic lean mass loss can occur in obesity whether or not patients are on obesity medications. As evidence of this, Dr. Kushner cited a subanalysis of the Look AHEAD trial of 1019 overweight or obese patients who had a mean age of 58 years at baseline. Patients were randomized to either a physical activity and reduced calorie intervention group or simply education.

Although the results showed that fat losses in the intervention group were generally regained over 8 years, a striking, steady decline was observed in lean mass in both the intervention and control groups, including men and women.

Dr. Fitch disclosed ties to Eli Lilly, Novo Nordisk, Currax, Vivus, SideKick Health, Jenny Craig, Carmot, and Seca. Dr. Kushner is on the advisory boards of Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

Food and drink advertisements on video game live-streaming platforms (VGLSPs) such as Twitch are associated with a greater preference for and consumption of products high in fat, salt, and/or sugar (HFSS) among teenagers, according to research presented on May 12, 2024, at the 31st European Congress on Obesity in Venice, Italy.

The presentation by Rebecca Evans, University of Liverpool, United Kingdom, included findings from three recently published studies and a submitted randomized controlled trial. At the time of the research, the top VGLSPs globally were Twitch (with 77% of the market share by hours watched), YouTube Gaming (15%), and Facebook Gaming Live (7%).

“Endorsement deals for prominent streamers on Twitch can be worth many millions of dollars, and younger people, who are attractive to advertisers, are moving away from television to these more interactive forms of entertainment,” Evans said. “These deals involve collaborating with brands and promoting their products, including foods that are high in fats, salt, and/or sugar.”

To delve more deeply into the extent and consequences of VGLSP advertising for HFSS, the researchers first analyzed 52 hour-long Twitch videos uploaded to gaming platforms by three popular influencers. They found that food cues appeared at an average rate of 2.6 per hour, and the average duration of each cue was 20 minutes.

Most cues (70.7%) were for branded HFSS (80.5%), led by energy drinks (62.4%). Most (97.7%) were not accompanied by an advertising disclosure. Most food cues were either product placement (44.0%) and looping banners (40.6%) or features such as tie-ins, logos, or offers. Notably, these forms of advertising are always visible on the video game screen, so viewers cannot skip over them or close them.

Next, the team did a systematic review and meta-analysis to assess the relationship between exposure to digital game-based or influencer food marketing with food-related outcomes. They found that young people were twice as likely to prefer foods displayed via digital game-based marketing, and that influencer and digital game-based marketing was associated with increased HFSS food consumption of about 37 additional calories in one sitting.

Researchers then surveyed 490 youngsters (mean age, 16.8 years; 70%, female) to explore associations between recall of food marketing of the top VGLSPs and food-related outcomes. Recall was associated with more positive attitudes towards HFSS foods and, in turn, the purchase and consumption of the marketed HFSS foods.

In addition, the researchers conducted a lab-based randomized controlled trial to explore associations between HFSS food marketing via a mock Twitch stream and subsequent snack intake. A total of 91 youngsters (average age, 18 years; 69% women) viewed the mock stream, which contained either an advertisement (an image overlaid on the video featuring a brand logo and product) for an HFSS food, or a non-branded food. They were then offered a snack. Acute exposure to HFSS food marketing was not associated with immediate consumption, but more habitual use of VGLSPs was associated with increased intake of the marketed snack.

The observational studies could not prove cause and effect, and may not be generalizable to all teens, the authors acknowledged. They also noted that some of the findings are based on self-report surveys, which can lead to recall bias and may have affected the results.

Nevertheless, Ms. Evans said, “The high level of exposure to digital marketing of unhealthy food could drive excess calorie consumption and weight gain, particularly in adolescents who are more susceptible to advertising. It is important that digital food marketing restrictions encompass innovative and emerging digital media such as VGLSPs.”

The research formed Ms. Evans’ PhD work, which is funded by the University of Liverpool. Evans and colleagues declared no conflicts of interest.

A version of this article appeared on Medscape.com .

Food and drink advertisements on video game live-streaming platforms (VGLSPs) such as Twitch are associated with a greater preference for and consumption of products high in fat, salt, and/or sugar (HFSS) among teenagers, according to research presented on May 12, 2024, at the 31st European Congress on Obesity in Venice, Italy.

The presentation by Rebecca Evans, University of Liverpool, United Kingdom, included findings from three recently published studies and a submitted randomized controlled trial. At the time of the research, the top VGLSPs globally were Twitch (with 77% of the market share by hours watched), YouTube Gaming (15%), and Facebook Gaming Live (7%).

“Endorsement deals for prominent streamers on Twitch can be worth many millions of dollars, and younger people, who are attractive to advertisers, are moving away from television to these more interactive forms of entertainment,” Evans said. “These deals involve collaborating with brands and promoting their products, including foods that are high in fats, salt, and/or sugar.”

To delve more deeply into the extent and consequences of VGLSP advertising for HFSS, the researchers first analyzed 52 hour-long Twitch videos uploaded to gaming platforms by three popular influencers. They found that food cues appeared at an average rate of 2.6 per hour, and the average duration of each cue was 20 minutes.

Most cues (70.7%) were for branded HFSS (80.5%), led by energy drinks (62.4%). Most (97.7%) were not accompanied by an advertising disclosure. Most food cues were either product placement (44.0%) and looping banners (40.6%) or features such as tie-ins, logos, or offers. Notably, these forms of advertising are always visible on the video game screen, so viewers cannot skip over them or close them.

Next, the team did a systematic review and meta-analysis to assess the relationship between exposure to digital game-based or influencer food marketing with food-related outcomes. They found that young people were twice as likely to prefer foods displayed via digital game-based marketing, and that influencer and digital game-based marketing was associated with increased HFSS food consumption of about 37 additional calories in one sitting.

Researchers then surveyed 490 youngsters (mean age, 16.8 years; 70%, female) to explore associations between recall of food marketing of the top VGLSPs and food-related outcomes. Recall was associated with more positive attitudes towards HFSS foods and, in turn, the purchase and consumption of the marketed HFSS foods.

In addition, the researchers conducted a lab-based randomized controlled trial to explore associations between HFSS food marketing via a mock Twitch stream and subsequent snack intake. A total of 91 youngsters (average age, 18 years; 69% women) viewed the mock stream, which contained either an advertisement (an image overlaid on the video featuring a brand logo and product) for an HFSS food, or a non-branded food. They were then offered a snack. Acute exposure to HFSS food marketing was not associated with immediate consumption, but more habitual use of VGLSPs was associated with increased intake of the marketed snack.

The observational studies could not prove cause and effect, and may not be generalizable to all teens, the authors acknowledged. They also noted that some of the findings are based on self-report surveys, which can lead to recall bias and may have affected the results.

Nevertheless, Ms. Evans said, “The high level of exposure to digital marketing of unhealthy food could drive excess calorie consumption and weight gain, particularly in adolescents who are more susceptible to advertising. It is important that digital food marketing restrictions encompass innovative and emerging digital media such as VGLSPs.”

The research formed Ms. Evans’ PhD work, which is funded by the University of Liverpool. Evans and colleagues declared no conflicts of interest.

A version of this article appeared on Medscape.com .

Food and drink advertisements on video game live-streaming platforms (VGLSPs) such as Twitch are associated with a greater preference for and consumption of products high in fat, salt, and/or sugar (HFSS) among teenagers, according to research presented on May 12, 2024, at the 31st European Congress on Obesity in Venice, Italy.

The presentation by Rebecca Evans, University of Liverpool, United Kingdom, included findings from three recently published studies and a submitted randomized controlled trial. At the time of the research, the top VGLSPs globally were Twitch (with 77% of the market share by hours watched), YouTube Gaming (15%), and Facebook Gaming Live (7%).

“Endorsement deals for prominent streamers on Twitch can be worth many millions of dollars, and younger people, who are attractive to advertisers, are moving away from television to these more interactive forms of entertainment,” Evans said. “These deals involve collaborating with brands and promoting their products, including foods that are high in fats, salt, and/or sugar.”

To delve more deeply into the extent and consequences of VGLSP advertising for HFSS, the researchers first analyzed 52 hour-long Twitch videos uploaded to gaming platforms by three popular influencers. They found that food cues appeared at an average rate of 2.6 per hour, and the average duration of each cue was 20 minutes.

Most cues (70.7%) were for branded HFSS (80.5%), led by energy drinks (62.4%). Most (97.7%) were not accompanied by an advertising disclosure. Most food cues were either product placement (44.0%) and looping banners (40.6%) or features such as tie-ins, logos, or offers. Notably, these forms of advertising are always visible on the video game screen, so viewers cannot skip over them or close them.

Next, the team did a systematic review and meta-analysis to assess the relationship between exposure to digital game-based or influencer food marketing with food-related outcomes. They found that young people were twice as likely to prefer foods displayed via digital game-based marketing, and that influencer and digital game-based marketing was associated with increased HFSS food consumption of about 37 additional calories in one sitting.

Researchers then surveyed 490 youngsters (mean age, 16.8 years; 70%, female) to explore associations between recall of food marketing of the top VGLSPs and food-related outcomes. Recall was associated with more positive attitudes towards HFSS foods and, in turn, the purchase and consumption of the marketed HFSS foods.

In addition, the researchers conducted a lab-based randomized controlled trial to explore associations between HFSS food marketing via a mock Twitch stream and subsequent snack intake. A total of 91 youngsters (average age, 18 years; 69% women) viewed the mock stream, which contained either an advertisement (an image overlaid on the video featuring a brand logo and product) for an HFSS food, or a non-branded food. They were then offered a snack. Acute exposure to HFSS food marketing was not associated with immediate consumption, but more habitual use of VGLSPs was associated with increased intake of the marketed snack.

The observational studies could not prove cause and effect, and may not be generalizable to all teens, the authors acknowledged. They also noted that some of the findings are based on self-report surveys, which can lead to recall bias and may have affected the results.

Nevertheless, Ms. Evans said, “The high level of exposure to digital marketing of unhealthy food could drive excess calorie consumption and weight gain, particularly in adolescents who are more susceptible to advertising. It is important that digital food marketing restrictions encompass innovative and emerging digital media such as VGLSPs.”

The research formed Ms. Evans’ PhD work, which is funded by the University of Liverpool. Evans and colleagues declared no conflicts of interest.

A version of this article appeared on Medscape.com .

DENVER — The ability to provide adolescents with highly effective anti-obesity medications that now carry approvals from the US Food and Drug Administration (FDA) and support in guidelines offers reassurance of their use; however, a reality check often awaits for clinicians in terms of challenges ranging from accessing and affording the medications to managing real and rumored side effects.

Weighing in on the issues, experts at Obesity Medicine (OMA) 2024 offered some key strategies and practice hacks for overcoming those hurdles.

The incentive to provide treatment with popular glucagon-like peptide 1 (GLP-1) drugs such as semaglutide or the dual glucose-dependent insulinotropic peptide (GIP) GLP-1 tirzepatide lies in the evidence that their high efficacy in promoting weight loss, and hence preventing metabolic syndrome, has benefits that far outweigh the potential side effects, said Alaina Vidmar, MD, in presenting at the meeting.

“We can look at all the evidence and without question acknowledge that the GLP-1s/GIP agonists are the most effective agents that we currently have, with the least heterogeneity in response, and the most high responders compared with other agents,” said Dr. Vidmar, an assistant professor of clinical pediatrics at the Keck School of Medicine of University of Southern California and director of obesity medicine and bariatric surgery at Children’s Hospital Los Angeles.

The strength of the evidence is reflected in the landmark American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity, which recommends that “pediatricians and other primary healthcare providers should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks and may offer adolescents 8 years old with obesity weight loss pharmacotherapy, according to medication indications, risks.”

The AAP guidance echoes the recommendations of the drug makers and FDA that “a combination of specific behavioral techniques within the context of family-based behavioral treatment and the use of pharmacotherapy may be necessary to prevent life-limiting complications over time.”

However, in real-world practice, with the various challenges in providing that intensive, comprehensive care, clinicians should be prepared to get creative: “We sometimes have to do the best we can with what we have because the watchful waiting approach is not effective and leads to more harm than good,” Dr. Vidmar said.
 

Facilitating Access

The ongoing reported shortages in the highly popular anti-obesity medications, as well as insurance denials and high costs, are among the leading obstacles, for adolescents and adults alike.

Dr. Vidmar noted that key strategies at her center, Children’s Hospital Los Angeles, have been essential, however, in helping at least facilitate the authorization process.

The center’s approach began with contacting all the payers the center has contracts with to determine which of their policies cover these medications for adults and pediatrics and which agents are covered.

“This took work on the front end, but it was worth it because it helped us understand the framework for what we were going to go up against every time that we prescribed these medications,” she said.

Furthermore, the center’s specialty pharmacy set up contracts to be able to provide the drugs within the institution.

While the strategy can’t entirely mitigate the ongoing distribution concerns, “our pharmacy is now able to share with our weight management program what GLP-1s are available so that we can be more efficient in our work,” Dr. Vidmar said.

The center also created a list of contacts to provide to patients and their families, detailing local pharmacies that were most likely to have the medications.

Another strategy Dr. Vidmar’s center has utilized to allow the timely implementation of a GLP-1 treatment plan while awaiting a drug to become available is to create an alternative protocol, for instance, using liraglutide when awaiting semaglutide.

“If we are unable to get the lower doses of a weekly agent for titration, we have a standard protocol to bridge instead with liraglutide, and our patients, pharmacies, and even our authorizations are aware of the protocol,” Dr. Vidmar said.

“We often do not have a lot of control or agency over the distribution concerns; however, we can be thoughtful within our programs about how we titrate patients up to their full doses,” Dr. Vidmar said.
 

Mitigating Side Effects

When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Dr. Vidmar noted.

“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.

Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”

Dr. Vidmar shared a handout her center issues with key recommendations for mitigating GI effects in youth. These include:

• Eat smaller meals and eat slower
• Eat about half of what you usually eat
• Take about 15-20 minutes to eat your meal
• Aim for 60 g of protein per day
• Add fruits, vegetables, whole grains, and lean proteins to meals
• Limit foods that are spicy, greasy, or fried
• Drink water instead of sweet drinks

Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Dr. Vidmar said.

Regarding the GI effects, Dr. Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
 

Mood Concerns?

Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.

Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
 

Concurrent Psychiatric Pharmacotherapy

Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.

Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.

In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.

The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”

First author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”

Dr. Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”

“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.

To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Dr. Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”

However, the newer anti-obesity medications could prove to be important in those cases, Dr. Vidmar added.

“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”

Dr. Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Dr. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — The ability to provide adolescents with highly effective anti-obesity medications that now carry approvals from the US Food and Drug Administration (FDA) and support in guidelines offers reassurance of their use; however, a reality check often awaits for clinicians in terms of challenges ranging from accessing and affording the medications to managing real and rumored side effects.

Weighing in on the issues, experts at Obesity Medicine (OMA) 2024 offered some key strategies and practice hacks for overcoming those hurdles.

The incentive to provide treatment with popular glucagon-like peptide 1 (GLP-1) drugs such as semaglutide or the dual glucose-dependent insulinotropic peptide (GIP) GLP-1 tirzepatide lies in the evidence that their high efficacy in promoting weight loss, and hence preventing metabolic syndrome, has benefits that far outweigh the potential side effects, said Alaina Vidmar, MD, in presenting at the meeting.

“We can look at all the evidence and without question acknowledge that the GLP-1s/GIP agonists are the most effective agents that we currently have, with the least heterogeneity in response, and the most high responders compared with other agents,” said Dr. Vidmar, an assistant professor of clinical pediatrics at the Keck School of Medicine of University of Southern California and director of obesity medicine and bariatric surgery at Children’s Hospital Los Angeles.

The strength of the evidence is reflected in the landmark American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity, which recommends that “pediatricians and other primary healthcare providers should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks and may offer adolescents 8 years old with obesity weight loss pharmacotherapy, according to medication indications, risks.”

The AAP guidance echoes the recommendations of the drug makers and FDA that “a combination of specific behavioral techniques within the context of family-based behavioral treatment and the use of pharmacotherapy may be necessary to prevent life-limiting complications over time.”

However, in real-world practice, with the various challenges in providing that intensive, comprehensive care, clinicians should be prepared to get creative: “We sometimes have to do the best we can with what we have because the watchful waiting approach is not effective and leads to more harm than good,” Dr. Vidmar said.
 

Facilitating Access

The ongoing reported shortages in the highly popular anti-obesity medications, as well as insurance denials and high costs, are among the leading obstacles, for adolescents and adults alike.

Dr. Vidmar noted that key strategies at her center, Children’s Hospital Los Angeles, have been essential, however, in helping at least facilitate the authorization process.

The center’s approach began with contacting all the payers the center has contracts with to determine which of their policies cover these medications for adults and pediatrics and which agents are covered.

“This took work on the front end, but it was worth it because it helped us understand the framework for what we were going to go up against every time that we prescribed these medications,” she said.

Furthermore, the center’s specialty pharmacy set up contracts to be able to provide the drugs within the institution.

While the strategy can’t entirely mitigate the ongoing distribution concerns, “our pharmacy is now able to share with our weight management program what GLP-1s are available so that we can be more efficient in our work,” Dr. Vidmar said.

The center also created a list of contacts to provide to patients and their families, detailing local pharmacies that were most likely to have the medications.

Another strategy Dr. Vidmar’s center has utilized to allow the timely implementation of a GLP-1 treatment plan while awaiting a drug to become available is to create an alternative protocol, for instance, using liraglutide when awaiting semaglutide.

“If we are unable to get the lower doses of a weekly agent for titration, we have a standard protocol to bridge instead with liraglutide, and our patients, pharmacies, and even our authorizations are aware of the protocol,” Dr. Vidmar said.

“We often do not have a lot of control or agency over the distribution concerns; however, we can be thoughtful within our programs about how we titrate patients up to their full doses,” Dr. Vidmar said.
 

Mitigating Side Effects

When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Dr. Vidmar noted.

“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.

Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”

Dr. Vidmar shared a handout her center issues with key recommendations for mitigating GI effects in youth. These include:

• Eat smaller meals and eat slower
• Eat about half of what you usually eat
• Take about 15-20 minutes to eat your meal
• Aim for 60 g of protein per day
• Add fruits, vegetables, whole grains, and lean proteins to meals
• Limit foods that are spicy, greasy, or fried
• Drink water instead of sweet drinks

Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Dr. Vidmar said.

Regarding the GI effects, Dr. Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
 

Mood Concerns?

Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.

Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
 

Concurrent Psychiatric Pharmacotherapy

Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.

Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.

In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.

The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”

First author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”

Dr. Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”

“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.

To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Dr. Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”

However, the newer anti-obesity medications could prove to be important in those cases, Dr. Vidmar added.

“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”

Dr. Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Dr. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

DENVER — The ability to provide adolescents with highly effective anti-obesity medications that now carry approvals from the US Food and Drug Administration (FDA) and support in guidelines offers reassurance of their use; however, a reality check often awaits for clinicians in terms of challenges ranging from accessing and affording the medications to managing real and rumored side effects.

Weighing in on the issues, experts at Obesity Medicine (OMA) 2024 offered some key strategies and practice hacks for overcoming those hurdles.

The incentive to provide treatment with popular glucagon-like peptide 1 (GLP-1) drugs such as semaglutide or the dual glucose-dependent insulinotropic peptide (GIP) GLP-1 tirzepatide lies in the evidence that their high efficacy in promoting weight loss, and hence preventing metabolic syndrome, has benefits that far outweigh the potential side effects, said Alaina Vidmar, MD, in presenting at the meeting.

“We can look at all the evidence and without question acknowledge that the GLP-1s/GIP agonists are the most effective agents that we currently have, with the least heterogeneity in response, and the most high responders compared with other agents,” said Dr. Vidmar, an assistant professor of clinical pediatrics at the Keck School of Medicine of University of Southern California and director of obesity medicine and bariatric surgery at Children’s Hospital Los Angeles.

The strength of the evidence is reflected in the landmark American Academy of Pediatrics (AAP) Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity, which recommends that “pediatricians and other primary healthcare providers should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks and may offer adolescents 8 years old with obesity weight loss pharmacotherapy, according to medication indications, risks.”

The AAP guidance echoes the recommendations of the drug makers and FDA that “a combination of specific behavioral techniques within the context of family-based behavioral treatment and the use of pharmacotherapy may be necessary to prevent life-limiting complications over time.”

However, in real-world practice, with the various challenges in providing that intensive, comprehensive care, clinicians should be prepared to get creative: “We sometimes have to do the best we can with what we have because the watchful waiting approach is not effective and leads to more harm than good,” Dr. Vidmar said.
 

Facilitating Access

The ongoing reported shortages in the highly popular anti-obesity medications, as well as insurance denials and high costs, are among the leading obstacles, for adolescents and adults alike.

Dr. Vidmar noted that key strategies at her center, Children’s Hospital Los Angeles, have been essential, however, in helping at least facilitate the authorization process.

The center’s approach began with contacting all the payers the center has contracts with to determine which of their policies cover these medications for adults and pediatrics and which agents are covered.

“This took work on the front end, but it was worth it because it helped us understand the framework for what we were going to go up against every time that we prescribed these medications,” she said.

Furthermore, the center’s specialty pharmacy set up contracts to be able to provide the drugs within the institution.

While the strategy can’t entirely mitigate the ongoing distribution concerns, “our pharmacy is now able to share with our weight management program what GLP-1s are available so that we can be more efficient in our work,” Dr. Vidmar said.

The center also created a list of contacts to provide to patients and their families, detailing local pharmacies that were most likely to have the medications.

Another strategy Dr. Vidmar’s center has utilized to allow the timely implementation of a GLP-1 treatment plan while awaiting a drug to become available is to create an alternative protocol, for instance, using liraglutide when awaiting semaglutide.

“If we are unable to get the lower doses of a weekly agent for titration, we have a standard protocol to bridge instead with liraglutide, and our patients, pharmacies, and even our authorizations are aware of the protocol,” Dr. Vidmar said.

“We often do not have a lot of control or agency over the distribution concerns; however, we can be thoughtful within our programs about how we titrate patients up to their full doses,” Dr. Vidmar said.
 

Mitigating Side Effects

When the medications are available, the common gastrointestinal (GI) side effects of nausea, vomiting, and diarrhea of the once-weekly injections are well-known, and these side effects can affect quality of life and daily function, Dr. Vidmar noted.

“We have to acknowledge that the seminal trials of these agents showed that nausea and vomiting occur in more than half of young people who take these agents during the initial titration period, and while the side effects are tolerated by many, they can be disruptive to daily life,” she said.

Encouragingly, “we also do know that for the majority of patients, those effects improve over time, and for many, they can be mitigated with nutrition changes.”

Dr. Vidmar shared a handout her center issues with key recommendations for mitigating GI effects in youth. These include:

• Eat smaller meals and eat slower
• Eat about half of what you usually eat
• Take about 15-20 minutes to eat your meal
• Aim for 60 g of protein per day
• Add fruits, vegetables, whole grains, and lean proteins to meals
• Limit foods that are spicy, greasy, or fried
• Drink water instead of sweet drinks

Consider Zofran as needed during the titration period for GI symptoms. “We’ve started using this at our institution and are teaching patients how to use it; it can really help mitigate any ER visits when there is any vomiting by educating patients and families and providing appropriate expectations, and that has been very helpful,” Dr. Vidmar said.

Regarding the GI effects, Dr. Vidmar noted she has observed that tirzepatide use (though still off-label) in youths “tends to have milder GI side effects among younger people.”
 

Mood Concerns?

Another concern that has emerged in public discussion regarding side effects is that of possible mood and suicidal ideation, raising concerns for adults and adolescents alike.

Upon investigating the reports, the FDA, in a statement, offered cautious reassurance that their review, including reports and clinical trials, “did not find an association between use of GLP-1 RAs and the occurrence of suicidal thoughts or actions.”

Noting that the agency is continuing to look into the issue, however, the FDA recommends that “healthcare professionals should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.”
 

Concurrent Psychiatric Pharmacotherapy

Meanwhile, with weight gain a known and often challenging side effect of various psychiatric drugs, particularly in younger patients, obesity treatment of adolescents may commonly involve patients who are also being treated with those therapies.

Key culprits include certain antidepressants and antipsychotic medications, such as tricyclic antidepressants, and second-generation antipsychotics, such as olanzapine.

In terms of the use of GLP-1 medications for those patients, research includes a recent study of semaglutide in patients who were also being treated with antidepressants.

The study, a post hoc analysis of the STEP trials, showed “clinically meaningful weight loss regardless of baseline antidepressant use, with an adverse event profile consistent with previous studies.”

First author Robert F. Kushner, MD, said the study offers “reassurance that individuals who are taking antidepressant medications have a similar weight loss response and side-effect profile compared to individuals who are not taking these medications.”

Dr. Kushner, a professor of medicine and medicine education at Northwestern University in Chicago, and his team have not evaluated the safety profile for concomitant use with antipsychotic drugs. However, he noted that “there are studies showing that the daily GLP-1 drug liraglutide has been shown to be useful in combating antipsychotic-induced weight gain.”

“Similar studies will need to be conducted for the more effective agents, semaglutide and tirzepatide,” he said.

To counter the weight gain effects of antispychotics, metformin has long been a standard recommendation, and Dr. Vidmar noted that “I have historically always used metformin in this setting and found it very effective.”

However, the newer anti-obesity medications could prove to be important in those cases, Dr. Vidmar added.

“I do think and predict that GLP-1 agonists will be as effective, if not more, in combating the weight gain-promoting effects of these agents and act as a nice adjuvant to this treatment paradigm for psychiatrists.”

Dr. Vidmar has participated in an advisory board for Rhythm Pharmaceuticals. Dr. Kushner is on the advisory boards for Novo Nordisk, Weight Watchers, Lilly, Boehringer Ingelheim, and Altimmune.

A version of this article appeared on Medscape.com.

Let’s be honest: Although as physicians we have the power of the prescription pad, so much of health, in the end, comes down to lifestyle. Of course, taking a pill is often way easier than changing your longstanding habits. And what’s worse, doesn’t it always seem like the lifestyle stuff that is good for your health is unpleasant?

Two recent lifestyle interventions that I have tried and find really not enjoyable are time-restricted eating (also known as intermittent fasting) and high-intensity interval training, or HIIT. The former leaves me hangry for half the day; the latter is, well, it’s just really hard compared with my usual jog.

Yale University

But given the rule of unpleasant lifestyle changes, I knew as soon as I saw this recent study what the result would be. What if we combined time-restricted eating with high-intensity interval training?

I’m referring to this study, appearing in PLOS ONE from Ranya Ameur and colleagues, which is a small trial that enrolled otherwise healthy women with a BMI > 30 and randomized them to one of three conditions.

First was time-restricted eating. Women in this group could eat whatever they wanted, but only from 8 a.m. to 4 p.m. daily.

Second: high-intensity functional training. This is a variant of high-intensity interval training which focuses a bit more on resistance exercise than on pure cardiovascular stuff but has the same vibe of doing brief bursts of intensive activity followed by a cool-down period.

Third: a combination of the two. Sounds rough to me.

The study was otherwise straightforward. At baseline, researchers collected data on body composition and dietary intake, and measured blood pressure, glucose, insulin, and lipid biomarkers. A 12-week intervention period followed, after which all of this stuff was measured again.

Now, you may have noticed that there is no control group in this study. We’ll come back to that — a few times.

Let me walk you through some of the outcomes here.

First off, body composition metrics. All three groups lost weight — on average, around 10% of body weight which, for a 12-week intervention, is fairly impressive. BMI and waist circumference went down as well, and, interestingly, much of the weight loss here was in fat mass, not fat-free mass.

Most interventions that lead to weight loss — and I’m including some of the newer drugs here — lead to both fat and muscle loss. That might not be as bad as it sounds; the truth is that muscle mass increases as fat increases because of the simple fact that if you’re carrying more weight when you walk around, your leg muscles get bigger. But to preserve muscle mass in the face of fat loss is sort of a Goldilocks finding, and, based on these results, there’s a suggestion that the high-intensity functional training helps to do just that.

The dietary intake findings were really surprising to me. Across the board, caloric intake decreased. It’s no surprise that time-restricted eating reduces calorie intake. That has been shown many times before and is probably the main reason it induces weight loss — less time to eat means you eat less.

But why would high-intensity functional training lead to lower caloric intake? Most people, myself included, get hungry after they exercise. In fact, one of the reasons it’s hard to lose weight with exercise alone is that we end up eating more calories to make up for what we lost during the exercise. This calorie reduction could be a unique effect of this type of exercise, but honestly this could also be something called the Hawthorne effect. Women in the study kept a food diary to track their intake, and the act of doing that might actually make you eat less. It makes it a little more annoying to snack a bit if you know you have to write it down. This is a situation where I would kill for a control group.

The lipid findings are also pretty striking, with around a 40% reduction in LDL across the board, and evidence of synergistic effects of combined TRE and high-intensity training on total cholesterol and triglycerides. This is like a statin level of effect — pretty impressive. Again, my heart pines for a control group, though.

Same story with glucose and insulin measures: an impressive reduction in fasting glucose and good evidence that the combination of time-restricted eating and high-intensity functional training reduces insulin levels and HOMA-IR as well.

Really the only thing that wasn’t very impressive was the change in blood pressure, with only modest decreases across the board.

Okay, so let’s take a breath after this high-intensity cerebral workout and put this all together. This was a small study, lacking a control group, but with large effect sizes in very relevant clinical areas. It confirms what we know about time-restricted eating — that it makes you eat less calories — and introduces the potential that vigorous exercise can not only magnify the benefits of time-restricted eating but maybe even mitigate some of the risks, like the risk for muscle loss. And of course, it comports with my central hypothesis, which is that the more unpleasant a lifestyle intervention is, the better it is for you. No pain, no gain, right?

Of course, I am being overly dogmatic. There are plenty of caveats. Wrestling bears is quite unpleasant and almost certainly bad for you. And there are even some pleasant things that are pretty good for you — like coffee and sex. And there are even people who find time-restricted eating and high-intensity training pleasurable. They are called masochists.

I’m joking. The truth is that any lifestyle change is hard, but with persistence the changes become habits and, eventually, those habits do become pleasurable. Or, at least, much less painful. The trick is getting over the hump of change. If only there were a pill for that.
 

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.

A version of this article appeared on Medscape.com.

Let’s be honest: Although as physicians we have the power of the prescription pad, so much of health, in the end, comes down to lifestyle. Of course, taking a pill is often way easier than changing your longstanding habits. And what’s worse, doesn’t it always seem like the lifestyle stuff that is good for your health is unpleasant?

Two recent lifestyle interventions that I have tried and find really not enjoyable are time-restricted eating (also known as intermittent fasting) and high-intensity interval training, or HIIT. The former leaves me hangry for half the day; the latter is, well, it’s just really hard compared with my usual jog.

Yale University

But given the rule of unpleasant lifestyle changes, I knew as soon as I saw this recent study what the result would be. What if we combined time-restricted eating with high-intensity interval training?

I’m referring to this study, appearing in PLOS ONE from Ranya Ameur and colleagues, which is a small trial that enrolled otherwise healthy women with a BMI > 30 and randomized them to one of three conditions.

First was time-restricted eating. Women in this group could eat whatever they wanted, but only from 8 a.m. to 4 p.m. daily.

Second: high-intensity functional training. This is a variant of high-intensity interval training which focuses a bit more on resistance exercise than on pure cardiovascular stuff but has the same vibe of doing brief bursts of intensive activity followed by a cool-down period.

Third: a combination of the two. Sounds rough to me.

The study was otherwise straightforward. At baseline, researchers collected data on body composition and dietary intake, and measured blood pressure, glucose, insulin, and lipid biomarkers. A 12-week intervention period followed, after which all of this stuff was measured again.

Now, you may have noticed that there is no control group in this study. We’ll come back to that — a few times.

Let me walk you through some of the outcomes here.

First off, body composition metrics. All three groups lost weight — on average, around 10% of body weight which, for a 12-week intervention, is fairly impressive. BMI and waist circumference went down as well, and, interestingly, much of the weight loss here was in fat mass, not fat-free mass.

Most interventions that lead to weight loss — and I’m including some of the newer drugs here — lead to both fat and muscle loss. That might not be as bad as it sounds; the truth is that muscle mass increases as fat increases because of the simple fact that if you’re carrying more weight when you walk around, your leg muscles get bigger. But to preserve muscle mass in the face of fat loss is sort of a Goldilocks finding, and, based on these results, there’s a suggestion that the high-intensity functional training helps to do just that.

The dietary intake findings were really surprising to me. Across the board, caloric intake decreased. It’s no surprise that time-restricted eating reduces calorie intake. That has been shown many times before and is probably the main reason it induces weight loss — less time to eat means you eat less.

But why would high-intensity functional training lead to lower caloric intake? Most people, myself included, get hungry after they exercise. In fact, one of the reasons it’s hard to lose weight with exercise alone is that we end up eating more calories to make up for what we lost during the exercise. This calorie reduction could be a unique effect of this type of exercise, but honestly this could also be something called the Hawthorne effect. Women in the study kept a food diary to track their intake, and the act of doing that might actually make you eat less. It makes it a little more annoying to snack a bit if you know you have to write it down. This is a situation where I would kill for a control group.

The lipid findings are also pretty striking, with around a 40% reduction in LDL across the board, and evidence of synergistic effects of combined TRE and high-intensity training on total cholesterol and triglycerides. This is like a statin level of effect — pretty impressive. Again, my heart pines for a control group, though.

Same story with glucose and insulin measures: an impressive reduction in fasting glucose and good evidence that the combination of time-restricted eating and high-intensity functional training reduces insulin levels and HOMA-IR as well.

Really the only thing that wasn’t very impressive was the change in blood pressure, with only modest decreases across the board.

Okay, so let’s take a breath after this high-intensity cerebral workout and put this all together. This was a small study, lacking a control group, but with large effect sizes in very relevant clinical areas. It confirms what we know about time-restricted eating — that it makes you eat less calories — and introduces the potential that vigorous exercise can not only magnify the benefits of time-restricted eating but maybe even mitigate some of the risks, like the risk for muscle loss. And of course, it comports with my central hypothesis, which is that the more unpleasant a lifestyle intervention is, the better it is for you. No pain, no gain, right?

Of course, I am being overly dogmatic. There are plenty of caveats. Wrestling bears is quite unpleasant and almost certainly bad for you. And there are even some pleasant things that are pretty good for you — like coffee and sex. And there are even people who find time-restricted eating and high-intensity training pleasurable. They are called masochists.

I’m joking. The truth is that any lifestyle change is hard, but with persistence the changes become habits and, eventually, those habits do become pleasurable. Or, at least, much less painful. The trick is getting over the hump of change. If only there were a pill for that.
 

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.

A version of this article appeared on Medscape.com.

Let’s be honest: Although as physicians we have the power of the prescription pad, so much of health, in the end, comes down to lifestyle. Of course, taking a pill is often way easier than changing your longstanding habits. And what’s worse, doesn’t it always seem like the lifestyle stuff that is good for your health is unpleasant?

Two recent lifestyle interventions that I have tried and find really not enjoyable are time-restricted eating (also known as intermittent fasting) and high-intensity interval training, or HIIT. The former leaves me hangry for half the day; the latter is, well, it’s just really hard compared with my usual jog.

Yale University

But given the rule of unpleasant lifestyle changes, I knew as soon as I saw this recent study what the result would be. What if we combined time-restricted eating with high-intensity interval training?

I’m referring to this study, appearing in PLOS ONE from Ranya Ameur and colleagues, which is a small trial that enrolled otherwise healthy women with a BMI > 30 and randomized them to one of three conditions.

First was time-restricted eating. Women in this group could eat whatever they wanted, but only from 8 a.m. to 4 p.m. daily.

Second: high-intensity functional training. This is a variant of high-intensity interval training which focuses a bit more on resistance exercise than on pure cardiovascular stuff but has the same vibe of doing brief bursts of intensive activity followed by a cool-down period.

Third: a combination of the two. Sounds rough to me.

The study was otherwise straightforward. At baseline, researchers collected data on body composition and dietary intake, and measured blood pressure, glucose, insulin, and lipid biomarkers. A 12-week intervention period followed, after which all of this stuff was measured again.

Now, you may have noticed that there is no control group in this study. We’ll come back to that — a few times.

Let me walk you through some of the outcomes here.

First off, body composition metrics. All three groups lost weight — on average, around 10% of body weight which, for a 12-week intervention, is fairly impressive. BMI and waist circumference went down as well, and, interestingly, much of the weight loss here was in fat mass, not fat-free mass.

Most interventions that lead to weight loss — and I’m including some of the newer drugs here — lead to both fat and muscle loss. That might not be as bad as it sounds; the truth is that muscle mass increases as fat increases because of the simple fact that if you’re carrying more weight when you walk around, your leg muscles get bigger. But to preserve muscle mass in the face of fat loss is sort of a Goldilocks finding, and, based on these results, there’s a suggestion that the high-intensity functional training helps to do just that.

The dietary intake findings were really surprising to me. Across the board, caloric intake decreased. It’s no surprise that time-restricted eating reduces calorie intake. That has been shown many times before and is probably the main reason it induces weight loss — less time to eat means you eat less.

But why would high-intensity functional training lead to lower caloric intake? Most people, myself included, get hungry after they exercise. In fact, one of the reasons it’s hard to lose weight with exercise alone is that we end up eating more calories to make up for what we lost during the exercise. This calorie reduction could be a unique effect of this type of exercise, but honestly this could also be something called the Hawthorne effect. Women in the study kept a food diary to track their intake, and the act of doing that might actually make you eat less. It makes it a little more annoying to snack a bit if you know you have to write it down. This is a situation where I would kill for a control group.

The lipid findings are also pretty striking, with around a 40% reduction in LDL across the board, and evidence of synergistic effects of combined TRE and high-intensity training on total cholesterol and triglycerides. This is like a statin level of effect — pretty impressive. Again, my heart pines for a control group, though.

Same story with glucose and insulin measures: an impressive reduction in fasting glucose and good evidence that the combination of time-restricted eating and high-intensity functional training reduces insulin levels and HOMA-IR as well.

Really the only thing that wasn’t very impressive was the change in blood pressure, with only modest decreases across the board.

Okay, so let’s take a breath after this high-intensity cerebral workout and put this all together. This was a small study, lacking a control group, but with large effect sizes in very relevant clinical areas. It confirms what we know about time-restricted eating — that it makes you eat less calories — and introduces the potential that vigorous exercise can not only magnify the benefits of time-restricted eating but maybe even mitigate some of the risks, like the risk for muscle loss. And of course, it comports with my central hypothesis, which is that the more unpleasant a lifestyle intervention is, the better it is for you. No pain, no gain, right?

Of course, I am being overly dogmatic. There are plenty of caveats. Wrestling bears is quite unpleasant and almost certainly bad for you. And there are even some pleasant things that are pretty good for you — like coffee and sex. And there are even people who find time-restricted eating and high-intensity training pleasurable. They are called masochists.

I’m joking. The truth is that any lifestyle change is hard, but with persistence the changes become habits and, eventually, those habits do become pleasurable. Or, at least, much less painful. The trick is getting over the hump of change. If only there were a pill for that.
 

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships. This transcript has been edited for clarity.

A version of this article appeared on Medscape.com.

A recent study links waist size and a higher risk for asthma attack. After adjustments, the likelihood of asthma attacks was 1.06 times higher for every 5-cm increase in waist circumference in adults with asthma.

BMI Earlier Tied to Asthma

Previous research supports a link between increased body mass index (BMI) and asthma, but the association between abdominal obesity and asthma attacks has not been well studied.

The researchers in the current study reviewed data from the National Health and Nutrition Examination Survey for 5530 adults with asthma in the United States. Adults in the study were divided into groups based on whether they did or did not experience asthma attacks.

The median age of the study population was 43 years, the median waist circumference was 98.9 cm, and the median BMI was 28.50.
 

More Waist Inches = Asthma Attacks

Overall, patients who reported asthma attacks had a significantly higher waist circumference than those without asthma attacks (median, 102.6 cm vs 97.3 cm, P < .001).

The association between increased waist circumference and increased odds of asthma attack was significant across non-adjusted, minimally adjusted, and fully adjusted models (odds ratios, 1.7, 1.06, and 1.06, respectively). In fact, each 5-cm increase in waist circumference was associated with a 1.06 times higher likelihood of an asthma attack after full adjustment for BMI-defined obesity, age, gender, race/ethnicity, education, poverty income ratio, smoking status, and metabolic syndrome.

The relationship between increased likelihood of asthma attacks and increased waist circumference persisted in subgroup analyses based on gender, age, and smoking status.
 

Importance of Waist Size

“Our study underscores the critical role of waist circumference measurements in the routine health evaluations of individuals diagnosed with asthma, highlighting its inclusion as an essential aspect of comprehensive health assessments,” the researchers wrote.

Limited to Data Available

The study findings were limited by several factors including the use of existing database questions to evaluate asthma attacks, a lack of data on the specificity of triggers of asthma exacerbations, and an inability to distinguish the severity of asthma attacks.

The study was published online in BMC Public Health. The lead author was Xiang Liu, MD, of Qingdao Municipal Hospital, Qingdao, China.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A recent study links waist size and a higher risk for asthma attack. After adjustments, the likelihood of asthma attacks was 1.06 times higher for every 5-cm increase in waist circumference in adults with asthma.

BMI Earlier Tied to Asthma

Previous research supports a link between increased body mass index (BMI) and asthma, but the association between abdominal obesity and asthma attacks has not been well studied.

The researchers in the current study reviewed data from the National Health and Nutrition Examination Survey for 5530 adults with asthma in the United States. Adults in the study were divided into groups based on whether they did or did not experience asthma attacks.

The median age of the study population was 43 years, the median waist circumference was 98.9 cm, and the median BMI was 28.50.
 

More Waist Inches = Asthma Attacks

Overall, patients who reported asthma attacks had a significantly higher waist circumference than those without asthma attacks (median, 102.6 cm vs 97.3 cm, P < .001).

The association between increased waist circumference and increased odds of asthma attack was significant across non-adjusted, minimally adjusted, and fully adjusted models (odds ratios, 1.7, 1.06, and 1.06, respectively). In fact, each 5-cm increase in waist circumference was associated with a 1.06 times higher likelihood of an asthma attack after full adjustment for BMI-defined obesity, age, gender, race/ethnicity, education, poverty income ratio, smoking status, and metabolic syndrome.

The relationship between increased likelihood of asthma attacks and increased waist circumference persisted in subgroup analyses based on gender, age, and smoking status.
 

Importance of Waist Size

“Our study underscores the critical role of waist circumference measurements in the routine health evaluations of individuals diagnosed with asthma, highlighting its inclusion as an essential aspect of comprehensive health assessments,” the researchers wrote.

Limited to Data Available

The study findings were limited by several factors including the use of existing database questions to evaluate asthma attacks, a lack of data on the specificity of triggers of asthma exacerbations, and an inability to distinguish the severity of asthma attacks.

The study was published online in BMC Public Health. The lead author was Xiang Liu, MD, of Qingdao Municipal Hospital, Qingdao, China.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A recent study links waist size and a higher risk for asthma attack. After adjustments, the likelihood of asthma attacks was 1.06 times higher for every 5-cm increase in waist circumference in adults with asthma.

BMI Earlier Tied to Asthma

Previous research supports a link between increased body mass index (BMI) and asthma, but the association between abdominal obesity and asthma attacks has not been well studied.

The researchers in the current study reviewed data from the National Health and Nutrition Examination Survey for 5530 adults with asthma in the United States. Adults in the study were divided into groups based on whether they did or did not experience asthma attacks.

The median age of the study population was 43 years, the median waist circumference was 98.9 cm, and the median BMI was 28.50.
 

More Waist Inches = Asthma Attacks

Overall, patients who reported asthma attacks had a significantly higher waist circumference than those without asthma attacks (median, 102.6 cm vs 97.3 cm, P < .001).

The association between increased waist circumference and increased odds of asthma attack was significant across non-adjusted, minimally adjusted, and fully adjusted models (odds ratios, 1.7, 1.06, and 1.06, respectively). In fact, each 5-cm increase in waist circumference was associated with a 1.06 times higher likelihood of an asthma attack after full adjustment for BMI-defined obesity, age, gender, race/ethnicity, education, poverty income ratio, smoking status, and metabolic syndrome.

The relationship between increased likelihood of asthma attacks and increased waist circumference persisted in subgroup analyses based on gender, age, and smoking status.
 

Importance of Waist Size

“Our study underscores the critical role of waist circumference measurements in the routine health evaluations of individuals diagnosed with asthma, highlighting its inclusion as an essential aspect of comprehensive health assessments,” the researchers wrote.

Limited to Data Available

The study findings were limited by several factors including the use of existing database questions to evaluate asthma attacks, a lack of data on the specificity of triggers of asthma exacerbations, and an inability to distinguish the severity of asthma attacks.

The study was published online in BMC Public Health. The lead author was Xiang Liu, MD, of Qingdao Municipal Hospital, Qingdao, China.

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

People with diabetes don’t have higher gastric volumes than those without diabetes after following standard preoperative fasting instructions, suggested a study from a team of anesthesiologist researchers.

However, an endocrinologist faulted the study in part because the participants appeared to be healthier than typical populations with type 1 and type 2 diabetes. Moreover, the issue is now further complicated by the widespread use of glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of both type 2 diabetes and weight loss. These drugs, which were introduced after the study’s enrollment period, work in part by delaying gastric emptying.

The new data come from a prospective study of 84 people with diabetes (85% with type 2) and 96 without diabetes, all with a body mass index (BMI) < 40, who were undergoing elective surgery. A gastric ultrasound was used to assess their gastric contents after they had followed the standard preoperative fasting guidelines of stopping solids 8 hours prior to the procedure and clearing liquids 2 hours prior.

There was no significant difference between the two groups in gastric volume (0.81 mL/kg with diabetes vs 0.87 mL/kg without) or in the proportion with “full stomach,” as designated by the American Society of Anesthesiologists (ASA) guidelines (any solid content or > 1.5 mL/kg of clear fluid), which was seen in 13 with diabetes (15.5%) and 11 (11.5%) without.

Published in Anesthesiology, the findings offer reassurance that different fasting instructions generally aren’t needed for people with diabetes in order to minimize the risk for perioperative pulmonary aspiration, lead author Anahi Perlas, MD, professor of anesthesiology and pain medicine at the University of Toronto, told this news organization.

“We never change practice completely based on a single study, but I think in general, based on our findings, that most diabetic patients aren’t any different from nondiabetics when it comes to their gastric content after fasting, and our standard fasting instructions seem to be just as effective in ensuring an empty stomach.”

But, she added, “If someone has symptoms of gastroparesis or when in doubt, we can always do a gastric ultrasound exam at the bedside and see whether the stomach is full or empty ... it’s very quick, and it’s not difficult to do.”
 

Expert Identifies Noteworthy Study Limitations

In an accompanying editorial, Mark A. Warner, MD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, said the findings “will be very helpful to anesthesiologists,” although he noted that the exclusion of people with a BMI > 40 is a limitation.

However, Michael Horowitz, MBBS, PhD, FRACP, director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital and professor of medicine at Adelaide Medical School in Adelaide, Australia, disputed the study’s conclusions. He noted that the sample was small, and the participants had an average A1c of 7.2%. Fewer than half had microvascular or neuropathic complications. Thus, they were healthier than the general population with diabetes.

“They’ve picked the wrong group of diabetics,” said Dr. Horowitz, who specializes in gastrointestinal complications of diabetes. “This is not a group where you would expect a very high prevalence of delayed emptying.”

Gastric emptying of solids and liquids varies widely even among healthy people and more so in those with type 2 diabetes. About a third of those with above-target A1c levels have gastroparesis, while those more in the target range tend to have accelerated emptying, he explained.

And regarding the use of gastric ultrasound for those who are symptomatic, Dr. Horowitz said, “The relationship of symptoms such as nausea, vomiting, fullness, whatever it may be, with the rate of gastric emptying is weak at best. The association is not simply cause and effect.”
 

Are the Fasting Guidelines Flawed, Regardless of Diabetes Status?

Dr. Horowitz also faulted the ASA’s 2017 guidance revision for allowing clear liquids to be consumed up to 2 hours in advance of anesthesia because it doesn’t distinguish between liquids with and without calories.

“Whether you have diabetes or not, if you are allowed to have a sugar drink up to 2 hours before your operation, the majority of people empty at about 4 kcal/min, so they will still have some of that drink in their stomach,” he said. “If you want an empty stomach, the ASA guidelines are wrong.”

That explains why the study found relatively high rates of “full stomach” in both groups, 15.5% of those with diabetes and 11.5% of those without, he said.
 

The GLP-1 Agonist Factor

Although the study didn’t address GLP-1 receptor agonist use, Dr. Warner did in his accompanying editorial, noting that the drugs’ rapid expansion “will likely change how we use perioperative fasting guidelines. With these medications delaying gastric emptying times, we now have another risk factor for pulmonary aspiration to consider when applying fasting guidelines. The inconsistent impact of GLP-1 agonists on gastric emptying, ranging from little to significant, makes it difficult for anesthesiologists to gauge whether or not patients taking GLP-1 agonists are likely to have preoperative gastric liquid or solid contents that could cause subsequent damage if regurgitated.”

Gastric ultrasound can be helpful in this situation, Dr. Warner wrote. In addition, he endorsed the 2023 ASA guidance, which calls for withholding daily-dosed GLP-1 agonists on the day of the surgery and the weekly formulations for a week. And if gastrointestinal symptoms are present, delay elective procedures.

But Dr. Horowitz said those recommendations are likely insufficient as well, pointing to data suggesting that daily liraglutide can delay gastric emptying for up to 16 weeks in about a third of patients. Such studies haven’t been conducted by the manufacturers, particularly on the once-weekly formulations, and the ensuing risk for aspiration isn’t known.

“The slowing occurs in much lower doses than are used for glucose lowering,” Dr. Horowitz said. “It is very likely that plasma levels will need to be extremely low to avoid gastric slowing. The current guidelines fail to appreciate this. So, to withhold the short-acting drugs for 1 day is probably wrong. And to stop long-acting drugs for 1 week is almost certainly wrong too.”

But as for what should be done, he said, “I don’t actually know what you do about it. And no one does because there are no data available to answer the question.”

The study received funding from the Physicians’ Services Incorporated Foundation and the Canadian Society of Anesthesiologists. Dr. Perlas received support for nonclinical time through a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto, and the Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network. She is an executive editor of the journal Regional Anesthesia and Pain Medicine and does consulting work for FujiFilm SonoSite. Dr. Horowitz had no relevant disclosures.
 

A version of this article appeared on Medscape.com.