More children aged 12-15 years already have received at least one dose of a COVID-19 vaccine than have 16- and 17-year-olds, based on data from the Centers for Disease Control and Prevention.

As of May 30, almost 2.89 million children aged 12-15 years had received at least one dose, compared with nearly 2.73 million children aged 16-17, with those figures representing increases of 31.6% and 6.6% in the past week, respectively. Since the overall size of the 12-15 population is much larger, however, the proportion vaccinated is still smaller: 19.5% to 36.4%, according to the CDC’s COVID Data Tracker.

A look at full vaccination status shows that only 0.7% of those aged 12-15 years have received both doses of a two-dose vaccine or one dose of the single-shot variety, compared with 24% of those aged 16-17. For the country as a whole, 50.5% of all ages have received at least one dose and 40.7% are fully vaccinated, the CDC said.

Children aged 12-15 represent the largest share of the U.S. population (23.4%) initiating vaccination in the 14 days ending May 30, while children aged 16-17 made up just 4.5% of those getting their first dose. The younger group’s later entry into the vaccination pool shows up again when looking at completion rates, though, representing just 0.4% of all Americans who reached full vaccination during that same 14-day period, compared with 4.6% of the older children, the CDC data show.

Not all states are reporting data such as age for vaccine recipients, the CDC noted, and there are other variables that affect data collection. “Demographic data ... might differ by populations prioritized within each state or jurisdiction’s vaccination phase. Every geographic area has a different racial and ethnic composition, and not all are in the same vaccination phase,” the CDC said.

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More children aged 12-15 years already have received at least one dose of a COVID-19 vaccine than have 16- and 17-year-olds, based on data from the Centers for Disease Control and Prevention.

As of May 30, almost 2.89 million children aged 12-15 years had received at least one dose, compared with nearly 2.73 million children aged 16-17, with those figures representing increases of 31.6% and 6.6% in the past week, respectively. Since the overall size of the 12-15 population is much larger, however, the proportion vaccinated is still smaller: 19.5% to 36.4%, according to the CDC’s COVID Data Tracker.

A look at full vaccination status shows that only 0.7% of those aged 12-15 years have received both doses of a two-dose vaccine or one dose of the single-shot variety, compared with 24% of those aged 16-17. For the country as a whole, 50.5% of all ages have received at least one dose and 40.7% are fully vaccinated, the CDC said.

Children aged 12-15 represent the largest share of the U.S. population (23.4%) initiating vaccination in the 14 days ending May 30, while children aged 16-17 made up just 4.5% of those getting their first dose. The younger group’s later entry into the vaccination pool shows up again when looking at completion rates, though, representing just 0.4% of all Americans who reached full vaccination during that same 14-day period, compared with 4.6% of the older children, the CDC data show.

Not all states are reporting data such as age for vaccine recipients, the CDC noted, and there are other variables that affect data collection. “Demographic data ... might differ by populations prioritized within each state or jurisdiction’s vaccination phase. Every geographic area has a different racial and ethnic composition, and not all are in the same vaccination phase,” the CDC said.

[email protected]

More children aged 12-15 years already have received at least one dose of a COVID-19 vaccine than have 16- and 17-year-olds, based on data from the Centers for Disease Control and Prevention.

As of May 30, almost 2.89 million children aged 12-15 years had received at least one dose, compared with nearly 2.73 million children aged 16-17, with those figures representing increases of 31.6% and 6.6% in the past week, respectively. Since the overall size of the 12-15 population is much larger, however, the proportion vaccinated is still smaller: 19.5% to 36.4%, according to the CDC’s COVID Data Tracker.

A look at full vaccination status shows that only 0.7% of those aged 12-15 years have received both doses of a two-dose vaccine or one dose of the single-shot variety, compared with 24% of those aged 16-17. For the country as a whole, 50.5% of all ages have received at least one dose and 40.7% are fully vaccinated, the CDC said.

Children aged 12-15 represent the largest share of the U.S. population (23.4%) initiating vaccination in the 14 days ending May 30, while children aged 16-17 made up just 4.5% of those getting their first dose. The younger group’s later entry into the vaccination pool shows up again when looking at completion rates, though, representing just 0.4% of all Americans who reached full vaccination during that same 14-day period, compared with 4.6% of the older children, the CDC data show.

Not all states are reporting data such as age for vaccine recipients, the CDC noted, and there are other variables that affect data collection. “Demographic data ... might differ by populations prioritized within each state or jurisdiction’s vaccination phase. Every geographic area has a different racial and ethnic composition, and not all are in the same vaccination phase,” the CDC said.

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In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

Key clinical point: Patients with chronic pancreatitis, pancreatic cancer, and pancreatic resection, followed-up by a gastroenterologist had higher rates of screening for exocrine pancreatic insufficiency (EPI) and appropriate prescription of pancreatic enzyme replacement therapy (PERT).

Major finding: EPI screening by measurement of pancreatic elastase (odds ratio [OR], 5.94; P less than .001), PERT prescription (OR, 2.02; P less than .001), and prescription for a minimally effective dosage (OR, 1.5; P = .008) was higher in patients followed-up by gastroenterologist (n=470) vs. those who were not (n=994).

Study details: This retrospective study assessed 1,464 patients with either EPI, chronic pancreatitis, pancreatic cancer, or pancreatic resection at the University of Florida between February 2018 and February 2020.

Disclosures: No source of funding was identified.

Source: Ladna M et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)01015-5.

Key clinical point: Patients with chronic pancreatitis, pancreatic cancer, and pancreatic resection, followed-up by a gastroenterologist had higher rates of screening for exocrine pancreatic insufficiency (EPI) and appropriate prescription of pancreatic enzyme replacement therapy (PERT).

Major finding: EPI screening by measurement of pancreatic elastase (odds ratio [OR], 5.94; P less than .001), PERT prescription (OR, 2.02; P less than .001), and prescription for a minimally effective dosage (OR, 1.5; P = .008) was higher in patients followed-up by gastroenterologist (n=470) vs. those who were not (n=994).

Study details: This retrospective study assessed 1,464 patients with either EPI, chronic pancreatitis, pancreatic cancer, or pancreatic resection at the University of Florida between February 2018 and February 2020.

Disclosures: No source of funding was identified.

Source: Ladna M et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)01015-5.

Key clinical point: Patients with chronic pancreatitis, pancreatic cancer, and pancreatic resection, followed-up by a gastroenterologist had higher rates of screening for exocrine pancreatic insufficiency (EPI) and appropriate prescription of pancreatic enzyme replacement therapy (PERT).

Major finding: EPI screening by measurement of pancreatic elastase (odds ratio [OR], 5.94; P less than .001), PERT prescription (OR, 2.02; P less than .001), and prescription for a minimally effective dosage (OR, 1.5; P = .008) was higher in patients followed-up by gastroenterologist (n=470) vs. those who were not (n=994).

Study details: This retrospective study assessed 1,464 patients with either EPI, chronic pancreatitis, pancreatic cancer, or pancreatic resection at the University of Florida between February 2018 and February 2020.

Disclosures: No source of funding was identified.

Source: Ladna M et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)01015-5.

Key clinical point: Postoperative pancreas remnant volume was associated with the development of exocrine pancreatic insufficiency (EPI) after pancreatic resection.

Major finding: EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The incidence of EPI was higher in patients receiving Whipple vs. distal pancreatectomy (66% vs. 21%; P = .004). The only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% confidence interval, 0.88-0.98; P less than .01).

Study details: This study included 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45) at a single institution between 2017 and 2018.

Disclosures: No source of funding was identified.

Source: Johnston ME et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)02827-4.

Key clinical point: Postoperative pancreas remnant volume was associated with the development of exocrine pancreatic insufficiency (EPI) after pancreatic resection.

Major finding: EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The incidence of EPI was higher in patients receiving Whipple vs. distal pancreatectomy (66% vs. 21%; P = .004). The only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% confidence interval, 0.88-0.98; P less than .01).

Study details: This study included 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45) at a single institution between 2017 and 2018.

Disclosures: No source of funding was identified.

Source: Johnston ME et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)02827-4.

Key clinical point: Postoperative pancreas remnant volume was associated with the development of exocrine pancreatic insufficiency (EPI) after pancreatic resection.

Major finding: EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The incidence of EPI was higher in patients receiving Whipple vs. distal pancreatectomy (66% vs. 21%; P = .004). The only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% confidence interval, 0.88-0.98; P less than .01).

Study details: This study included 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45) at a single institution between 2017 and 2018.

Disclosures: No source of funding was identified.

Source: Johnston ME et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)02827-4.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Combining minimally invasive endoscopic sleeve gastroplasty with a weekly injection of the glucagonlike peptide–1 agonist semaglutide (Ozempic, Novo Nordisk) leads to significantly greater weight loss than ESG alone in patients with diabetes and excess weight who are not candidates for bariatric surgery, new research shows.

During minimally invasive ESG, a flexible endoscope equipped with an endoscopic suturing device is inserted down the esophagus and into the stomach. The endoscopist then applies the sutures to the upper portion of the stomach, minimizing its size to restrict the amount of food a patient can ingest.

“Our stomachs can stretch back a bit, but we can use the suturing device again,” explained the lead investigator of the research Anna Carolina Hoff, MD, founder and clinical director of Angioskope Brazil in São José dos Campos.

“It’s important that patients with diabetes lose as much weight as possible because, if they lose about 10% of their total body weight, they have a great improvement in their glycemic levels, and some patients can even stop taking their [antidiabetic] medications,” Dr. Hoff said in an interview.

“And we found that by adding the GLP-1 agonist [semaglutide], we could increase weight loss from, on average, about 16%-18% of total body weight with ESG alone to up to 27%, so it’s a great metabolic combination,” she noted.

Dr. Hoff presented the findings at the annual Digestive Disease Week® (DDW).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, George Washington University, Washington, cautioned that it’s still early days for minimally invasive ESG.

“It is reasonable to assume that the long-term outcomes [with ESG] won’t be as good or durable over time as with bariatric surgery, but ... we will have to see.”

However, “we know that, typically, combinations of therapeutic options work better than a one-off option, so I think the real benefit of this study – outside the specific procedure and this specific medication – is that it is a very valuable proof-of-principle study showing that combinations do work better,” Dr. Kahan said in an interview.
 

Minimally invasive endoscopic sleeve gastroplasty

ESG is a surrogate for laparoscopic sleeve gastrectomy that can offer the benefits of such a procedure to those who don’t qualify for, or don’t wish to pursue, bariatric surgery. It can be performed at an earlier stage of disease, in those with a body mass index of 30 mg/kg², whereas generally people are not offered bariatric procedures unless they have a BMI of at least 35 with comorbidities or a BMI of at least 40 if they do not have comorbidities.

Subcutaneous semaglutide is already approved for the treatment of type 2 diabetes in adults at doses of up to 1 mg/week; higher doses are needed for weight loss. Novo Nordisk has been investigating higher doses for weight loss in the STEP trial program, which is now complete, and the company has submitted the data to the Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) and who have at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity, with a decision expected soon.

Novo Nordisk has also developed an oral form of semaglutide, which has been approved as a once-daily agent for type 2 diabetes (Rybelsus) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
 

Patients lost fat mass as well as excess weight

The Brazilian study involved 58 patients with obesity or overweight who also had diabetes and were undergoing minimally invasive ESG; they were further randomized to receive semaglutide or placebo.

The GLP-1 agonist (or sham placebo) was initiated 1 month after participants had undergone the procedure and patients were monitored each month for weight loss and type of fat loss achieved with the combination versus ESG alone. The initial dose of semaglutide used was 0.25 mg subcutaneous a week but could be titrated up to a maximum dose of 1.5 mg.

At the end of 11 months of active treatment versus placebo (12 months after ESG), patients who received additional semaglutide lost 86.3% of their excess body weight – the amount of weight patients needed to lose to reach normal BMI – compared with only 60.4% for ESG controls.

Specifically, the mean percentage total body weight loss at the end of 12 months was 25.2% for those in the combination group, compared with 18.6% for those treated with ESG alone (P < .001).

More importantly, patients in the combination group lost 12.6% of their body fat mass, compared with 9% for ESG controls, while mean A1c levels fell more in those treated with additional semaglutide compared with controls (P = .0394).

Indeed, five patients in the combination group reverted to a nondiabetic state and were able to discontinue antidiabetic medications altogether, Dr. Hoff noted.

“Our main goal is not just to lose weight but to lose body mass fat, which is very different from just losing weight,” she explained.

If patients lose weight but still maintain a high percentage of body fat mass, they have what she refers to as “sarcopenic obesity” because in this state patients have lost a lot of muscle mass but still have high levels of metabolically active visceral fat. Among many other inflammatory complexes, metabolically active visceral fat contains a large number of inflammasomes, and it is the latter that have been associated with obesity-related cancers. 

“Obesity is a progressive disease, so what we are trying to do here is buy time for patients so they do not progress to [bariatric] surgery, and this approach gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur,” Dr. Hoff emphasized.

So, when combined with semaglutide, “we now have a minimally invasive procedure that can be just as successful [as surgery] and which can be made available to even more people looking to lose a significant amount of weight,” she concluded.

Dr. Hoff and Dr. Kahan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Key clinical point: Considerable proportion of patients suffer from exocrine pancreatic insufficiency (EPI)-associated complaints which persisted for 3 years or even more after pancreatoduodenectomy or left pancreatectomy, even in patients receiving pancreatic enzyme replacement therapy (PERT).

Major finding: EPI, indicated by PERT usage, was reported in 41% of patients, of which only 48% reported complete relief, whereas 35% reported decrease in EPI-related complaints. Patients with vs. without PERT had higher complaints of fatty stools (50% vs. 26%; P = .003) and unintentional weight loss (11% vs. 2%; P = .019).

Study details: This study included 153 patients who underwent pancreatoduodenectomy or left pancreatectomy for premalignant or benign diseases between 2006 and 2016.

Disclosures: This study was supported by the Dutch Cancer Society. The lead author reported research funding from Mylan and Allergan.

Source: Latenstein AEJ et al. HPB. 2021 Apr 27. doi: 10.1016/j.hpb.2021.04.012.

Key clinical point: Considerable proportion of patients suffer from exocrine pancreatic insufficiency (EPI)-associated complaints which persisted for 3 years or even more after pancreatoduodenectomy or left pancreatectomy, even in patients receiving pancreatic enzyme replacement therapy (PERT).

Major finding: EPI, indicated by PERT usage, was reported in 41% of patients, of which only 48% reported complete relief, whereas 35% reported decrease in EPI-related complaints. Patients with vs. without PERT had higher complaints of fatty stools (50% vs. 26%; P = .003) and unintentional weight loss (11% vs. 2%; P = .019).

Study details: This study included 153 patients who underwent pancreatoduodenectomy or left pancreatectomy for premalignant or benign diseases between 2006 and 2016.

Disclosures: This study was supported by the Dutch Cancer Society. The lead author reported research funding from Mylan and Allergan.

Source: Latenstein AEJ et al. HPB. 2021 Apr 27. doi: 10.1016/j.hpb.2021.04.012.

Key clinical point: Considerable proportion of patients suffer from exocrine pancreatic insufficiency (EPI)-associated complaints which persisted for 3 years or even more after pancreatoduodenectomy or left pancreatectomy, even in patients receiving pancreatic enzyme replacement therapy (PERT).

Major finding: EPI, indicated by PERT usage, was reported in 41% of patients, of which only 48% reported complete relief, whereas 35% reported decrease in EPI-related complaints. Patients with vs. without PERT had higher complaints of fatty stools (50% vs. 26%; P = .003) and unintentional weight loss (11% vs. 2%; P = .019).

Study details: This study included 153 patients who underwent pancreatoduodenectomy or left pancreatectomy for premalignant or benign diseases between 2006 and 2016.

Disclosures: This study was supported by the Dutch Cancer Society. The lead author reported research funding from Mylan and Allergan.

Source: Latenstein AEJ et al. HPB. 2021 Apr 27. doi: 10.1016/j.hpb.2021.04.012.

Key clinical point: Over half of the patients with childhood-onset hereditary pancreatitis developed exocrine pancreatic insufficiency (EPI). EPI development preceded loss of endocrine function in this rare patient population.

Major finding: Overall, EPI developed in 7 patients at an average age of 12.5±8.4 years, with fecal pancreatic elastase less than 100 mg/g in all patients at disease onset. No evidence of pancreoprive diabetes mellitus (type IIIc) was reported in any patient.

Study details: This retrospective study evaluated 11 patients with childhood-onset (mean age at onset, 7.5±4.2 years) hereditary pancreatitis.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Prommer R et al. Wien Klin Wochenschr. 2021 Apr 28. doi: 10.1007/s00508-021-01869-0.

Key clinical point: Over half of the patients with childhood-onset hereditary pancreatitis developed exocrine pancreatic insufficiency (EPI). EPI development preceded loss of endocrine function in this rare patient population.

Major finding: Overall, EPI developed in 7 patients at an average age of 12.5±8.4 years, with fecal pancreatic elastase less than 100 mg/g in all patients at disease onset. No evidence of pancreoprive diabetes mellitus (type IIIc) was reported in any patient.

Study details: This retrospective study evaluated 11 patients with childhood-onset (mean age at onset, 7.5±4.2 years) hereditary pancreatitis.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Prommer R et al. Wien Klin Wochenschr. 2021 Apr 28. doi: 10.1007/s00508-021-01869-0.

Key clinical point: Over half of the patients with childhood-onset hereditary pancreatitis developed exocrine pancreatic insufficiency (EPI). EPI development preceded loss of endocrine function in this rare patient population.

Major finding: Overall, EPI developed in 7 patients at an average age of 12.5±8.4 years, with fecal pancreatic elastase less than 100 mg/g in all patients at disease onset. No evidence of pancreoprive diabetes mellitus (type IIIc) was reported in any patient.

Study details: This retrospective study evaluated 11 patients with childhood-onset (mean age at onset, 7.5±4.2 years) hereditary pancreatitis.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Prommer R et al. Wien Klin Wochenschr. 2021 Apr 28. doi: 10.1007/s00508-021-01869-0.

Key clinical point: Although locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC) is associated with reduced exocrine function, there is a lack of clear guidelines for the diagnosis and management of exocrine pancreatic insufficiency (EPI) for palliative pancreatic ductal adenocarcinomas.

Major finding: Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively. Median body mass index decreased by 13.3% from preillness state to cancer diagnosis. Despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. Pancrelipase dose varied from 10,000 to 50,000 units with each meal.

Study details: This retrospective study assessed palliative management in 67 patients with LAPC or MPC.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Choi CCM et al. ANZ J Surg. 2021 Apr 18. doi: 10.1111/ans.16669.

Key clinical point: Although locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC) is associated with reduced exocrine function, there is a lack of clear guidelines for the diagnosis and management of exocrine pancreatic insufficiency (EPI) for palliative pancreatic ductal adenocarcinomas.

Major finding: Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively. Median body mass index decreased by 13.3% from preillness state to cancer diagnosis. Despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. Pancrelipase dose varied from 10,000 to 50,000 units with each meal.

Study details: This retrospective study assessed palliative management in 67 patients with LAPC or MPC.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Choi CCM et al. ANZ J Surg. 2021 Apr 18. doi: 10.1111/ans.16669.

Key clinical point: Although locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC) is associated with reduced exocrine function, there is a lack of clear guidelines for the diagnosis and management of exocrine pancreatic insufficiency (EPI) for palliative pancreatic ductal adenocarcinomas.

Major finding: Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively. Median body mass index decreased by 13.3% from preillness state to cancer diagnosis. Despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. Pancrelipase dose varied from 10,000 to 50,000 units with each meal.

Study details: This retrospective study assessed palliative management in 67 patients with LAPC or MPC.

Disclosures: No specific funding source was identified. The authors declared no conflicts of interest.

Source: Choi CCM et al. ANZ J Surg. 2021 Apr 18. doi: 10.1111/ans.16669.

Key clinical point: Patients with vs. without exocrine pancreatic insufficiency (EPI) had increased fasting breath hydrogen concentration (FBHC) levels, possibly because of the presence of hydrogen-producing genus Clostridium in the gut. FBHC may have a good potential as a simple test for EPI diagnosis.

Major finding: FBHC levels were significantly higher in the EPI vs. non-EPI (median, 15.70 ppm vs. 2.80 ppm; P less than .001) group and negatively correlated with p-aminobenzoic acid (PABA) excretion rate  (r, −0.523; P less than .001). The occupancy by Clostridia bacteria in intestinal bacterial flora was higher in EPI group (P less than .05).

Study details: This prospective study included 60 inpatients with pancreatic disease who underwent FBHC measurement, N-benzoyl-L-tyrosyl-PABA testing, and microbiome analysis. The PABA excretion rate of 73.4% classified patients into EPI (n=30) and non-EPI (n=30) groups.

Disclosures: No funding was obtained for this study. The authors declared no conflicts of interest.

Source: Uetsuki K et al. BMC Gastroenterol. 2021 May 10. doi: 10.1186/s12876-021-01776-8.

Key clinical point: Patients with vs. without exocrine pancreatic insufficiency (EPI) had increased fasting breath hydrogen concentration (FBHC) levels, possibly because of the presence of hydrogen-producing genus Clostridium in the gut. FBHC may have a good potential as a simple test for EPI diagnosis.

Major finding: FBHC levels were significantly higher in the EPI vs. non-EPI (median, 15.70 ppm vs. 2.80 ppm; P less than .001) group and negatively correlated with p-aminobenzoic acid (PABA) excretion rate  (r, −0.523; P less than .001). The occupancy by Clostridia bacteria in intestinal bacterial flora was higher in EPI group (P less than .05).

Study details: This prospective study included 60 inpatients with pancreatic disease who underwent FBHC measurement, N-benzoyl-L-tyrosyl-PABA testing, and microbiome analysis. The PABA excretion rate of 73.4% classified patients into EPI (n=30) and non-EPI (n=30) groups.

Disclosures: No funding was obtained for this study. The authors declared no conflicts of interest.

Source: Uetsuki K et al. BMC Gastroenterol. 2021 May 10. doi: 10.1186/s12876-021-01776-8.

Key clinical point: Patients with vs. without exocrine pancreatic insufficiency (EPI) had increased fasting breath hydrogen concentration (FBHC) levels, possibly because of the presence of hydrogen-producing genus Clostridium in the gut. FBHC may have a good potential as a simple test for EPI diagnosis.

Major finding: FBHC levels were significantly higher in the EPI vs. non-EPI (median, 15.70 ppm vs. 2.80 ppm; P less than .001) group and negatively correlated with p-aminobenzoic acid (PABA) excretion rate  (r, −0.523; P less than .001). The occupancy by Clostridia bacteria in intestinal bacterial flora was higher in EPI group (P less than .05).

Study details: This prospective study included 60 inpatients with pancreatic disease who underwent FBHC measurement, N-benzoyl-L-tyrosyl-PABA testing, and microbiome analysis. The PABA excretion rate of 73.4% classified patients into EPI (n=30) and non-EPI (n=30) groups.

Disclosures: No funding was obtained for this study. The authors declared no conflicts of interest.

Source: Uetsuki K et al. BMC Gastroenterol. 2021 May 10. doi: 10.1186/s12876-021-01776-8.

Key clinical point: Lumacaftor-ivacaftor treatment for 120 weeks improved exocrine pancreatic insufficiency and pancreatic damage in children as young as 2-5 years of age with cystic fibrosis (CF) homozygous for F508del-CF transmembrane conductance regulator gene.

Major finding: At baseline, 100% of participants had fecal elastase-1 (FE-1) less than 200 µg/g, of which 41 participants had FE-1 less than 15 µg/g. Treatment with lumacaftor-ivacaftor increased FE-1 (mean absolute change [D], 132.6±174.2 µg/g) and decreased immunoreactive trypsinogen (D, −108.5±306.6 ng/mL) from baseline to 120 weeks.

Study details: This phase 3 rollover trial (study 116) included 57 children with CF who completed 24 weeks of lumacaftor-ivacaftor treatment in previous study 115. Patients received weight- and age-based doses of lumacaftor-ivacaftor for additional 96 weeks, totaling 120 weeks of treatment.

Disclosures: This study was funded by Vertex Pharmaceuticals Incorporated (VPI). VPI was funded by CF Foundation for lumacaftor development. Some investigators including the lead author reported ties with VPI and CF Foundation.

Source: Hoppe JE et al. Lancet Respir Med. 2021 May 6. doi: 10.1016/S2213-2600(21)00069-2.

Key clinical point: Lumacaftor-ivacaftor treatment for 120 weeks improved exocrine pancreatic insufficiency and pancreatic damage in children as young as 2-5 years of age with cystic fibrosis (CF) homozygous for F508del-CF transmembrane conductance regulator gene.

Major finding: At baseline, 100% of participants had fecal elastase-1 (FE-1) less than 200 µg/g, of which 41 participants had FE-1 less than 15 µg/g. Treatment with lumacaftor-ivacaftor increased FE-1 (mean absolute change [D], 132.6±174.2 µg/g) and decreased immunoreactive trypsinogen (D, −108.5±306.6 ng/mL) from baseline to 120 weeks.

Study details: This phase 3 rollover trial (study 116) included 57 children with CF who completed 24 weeks of lumacaftor-ivacaftor treatment in previous study 115. Patients received weight- and age-based doses of lumacaftor-ivacaftor for additional 96 weeks, totaling 120 weeks of treatment.

Disclosures: This study was funded by Vertex Pharmaceuticals Incorporated (VPI). VPI was funded by CF Foundation for lumacaftor development. Some investigators including the lead author reported ties with VPI and CF Foundation.

Source: Hoppe JE et al. Lancet Respir Med. 2021 May 6. doi: 10.1016/S2213-2600(21)00069-2.

Key clinical point: Lumacaftor-ivacaftor treatment for 120 weeks improved exocrine pancreatic insufficiency and pancreatic damage in children as young as 2-5 years of age with cystic fibrosis (CF) homozygous for F508del-CF transmembrane conductance regulator gene.

Major finding: At baseline, 100% of participants had fecal elastase-1 (FE-1) less than 200 µg/g, of which 41 participants had FE-1 less than 15 µg/g. Treatment with lumacaftor-ivacaftor increased FE-1 (mean absolute change [D], 132.6±174.2 µg/g) and decreased immunoreactive trypsinogen (D, −108.5±306.6 ng/mL) from baseline to 120 weeks.

Study details: This phase 3 rollover trial (study 116) included 57 children with CF who completed 24 weeks of lumacaftor-ivacaftor treatment in previous study 115. Patients received weight- and age-based doses of lumacaftor-ivacaftor for additional 96 weeks, totaling 120 weeks of treatment.

Disclosures: This study was funded by Vertex Pharmaceuticals Incorporated (VPI). VPI was funded by CF Foundation for lumacaftor development. Some investigators including the lead author reported ties with VPI and CF Foundation.

Source: Hoppe JE et al. Lancet Respir Med. 2021 May 6. doi: 10.1016/S2213-2600(21)00069-2.