Once weekly semaglutide for treatment of obesity

Background: Once weekly (OW) semaglutide 0.5-1.0 mg is a glucagon-like type-1 receptor agonist (GLR-1 RA) approved for treatment of type 2 diabetes and is currently under evaluation for treatment of obesity at a higher dose of 2.4 mg OW. Objective: to provide an appraisal of WO semaglutide 2.4 mg for treatment of obesity. Methods: Pubmed research up to March 22. Randomized trials, pertinent animal studies, and reviews are included. Search terms were glucagon-like type 1 receptor agonists, weight loss, obesity, semaglutide, safety, efficacy. Results: WO semaglutide 2.4 mg was evaluated as a weight loss agent in 3 well-designed clinical trials of 68 week-duration. In one trial including patients with type 2 diabetes, the difference in weight loss from baseline to week 68 between OW semaglutide and placebo was - 6.2 percentage points (95% CI, -7.3 to -5.2; P<0.0001). In the other 2 studies that excluded patients with diabetes, the difference in weight loss between OW semaglutide and placebo ranged between -10.3% and -12.4%. A significantly higher proportion of participants in the semaglutide groups vs placebo groups achieved at least 5% of weight loss. The most common adverse effects of semaglutide were related to the gastrointestinal (GI) system. Across these 3 trials, premature discontinuation of OW semaglutide occurred in 6-7% vs 3% in placebo groups. Conclusions: OW semaglutide may be a promising agent for treatment of obesity irrespective of presence of type 2 diabetes. Further studies are needed to establish its long-term safety and efficacy.