Semaglutide Boosts Weight Loss Following Endoscopic Gastroplasty

Pam Harrison

May 27, 2021

Combining minimally invasive endoscopic sleeve gastroplasty (ESG) with a weekly injection of the glucagon-like peptide-1 (GLP-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, 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," Hoff told Medscape Medical News.

"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.

Hoff presented the findings during the virtual Digestive Disease Week 2021 (DDW 2021).

Asked to comment, Scott Kahan, MD, MPH, director, National Center for Weight and Wellness, Milken Institute School of Public Health, George Washington University, Washington, DC, 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," Kahan told Medscape Medical News.

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 (BMI) of 30 mg/kg2, whereas generally people are not offered bariatric procedures unless they have a BMI ≥ 35 mg/kg2 with comorbidities or a BMI ≥ 40 mg/kg2 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 US Food and Drug Administration and European Medicines Agency for an additional indication of adults with obesity (BMI ≥ 30 kg/m2) or who are overweight (BMI ≥ 27 kg/m2) 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 to 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, 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," she 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.

Hoff and Kahan have reported no relevant financial relationships.
DDW 2021. Abstract Su548. Presented May 23, 2012.

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