Semaglutide on top of ESG boosts weight loss in diabetes

Once-weekly injection of the GLP-1* agonist semaglutide, on top of endoscopic sleeve gastroplasty (ESG), led to a greater weight loss and better glucose control vs ESG alone in patients with diabetes and excess weight but are not candidates for bariatric surgery, a new study has shown.

“It’s important for patients with diabetes to lose weight because if they do,  they lose about 10 percent of their total body weight, and they will have great improvement in their glycaemic levels,” said lead investigator Dr Anna Carolina Hoff, clinical director of Angioskope Brazil, São José dos Campos, at DDW 2021. “Some patients can even stop taking their [antidiabetic] medications.”

“By adding semaglutide [to ESG], we could increase weight loss up to 27 percent of total body weight from about 16–18 percent with ESG alone. So, it’s a great metabolic combination,” she added.

Combo therapy works

ESG supposedly minimizes the stomach size to restrict the amount of food a patient can take in. But it still is early days for the procedure, commented Dr Scott Kahan, director at the National Center for Weight and Wellness, Milken Institute School of Public Health, George Washington University in Washington, DC.

“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, so we’ll have to see,” he said. “The real benefit is that this study provides a proof-of-concept that combination therapies actually work better.”  

Greater weight loss + lower HbA_1c

Patients were started on subcutaneous semaglutide 0.25 mg or placebo 1 month after ESG and then monitored for weight loss each month. Semaglutide could be titrated up to a maximum dose of 1.5 mg. Similar directives were given regarding diet and exercise.

After 11 months of active treatment, the percentage of excess weight loss was 86 percent with semaglutide and 60 percent with placebo(p<0.001). The mean percentage of total body weight loss at 12 months was 25.2 percent with semaglutide vs 18.6 percent with placebo (p<0.001). [DDW 2021, abstract Su548]

In addition, patients on semaglutide had a greater reduction in percent body fat mass (12.7 percent vs 9 percent with placebo; p<0.001). “Our main goal here is not just to lose weight but to lose body fat mass as well.”

Mean HbA_1c levels were also lower in those treated with semaglutide (p=0.0394). Amylase and lipase levels were unchanged. Interestingly, five patients treated with semaglutide after ESG reverted to a nondiabetic state and were able to discontinue their antidiabetic medications, Hoff added.

Buying time

“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,” she continued.

While bariatric surgery remains the gold standard for sustained weight loss, fewer than 2 percent of eligible patients pursue this option, added Hoff. “As the rate of worldwide obesity continues to climb, so does the number of people seeking more cost-effective alternative to surgery to treat their condition.”

Semaglutide, on top of ESG, gives patients a chance to act earlier before obesity takes over and more metabolic consequences occur, she concluded.