Semaglutide For Weight Loss – STEP 1 Trial
A new treatment for chronic weight management is likely on the way. In a recent trial, investigators looked at semaglutide for weight loss. The final results of the STEP1 trial (Semaglutide Treatment Effect in People with obesity) were recently reported in the New England Journal of Medicine. Semaglutide, a GLP-1 receptor agonist approved for type II diabetes treatment and reducing cardiovascular risk in these patients, was measured against placebo at once-weekly doses of over 2-fold those used in diabetes. Novo Nordisk applied for NDA approval of semaglutide 2.4mg for weight loss on 12/4/2020 so the FDA should likely rule on that by 6/4/2021.
In the double-blind, multicenter, international, randomized, controlled trial funded by Novo Nordisk, 1961 obese adults without diabetes demonstrated a 12.4% (28 pounds) greater average reduction in total body weight when assigned to semaglutide versus placebo after 68 weeks. All patients received diet and exercise coaching every 4 weeks. Additionally, over half of patients assigned to the active drug arm lost 15% or more of their original body weight compared to just 4.9% of those receiving placebo. Patients in the intervention group also experienced significant decreases in systolic blood pressure and increased physical function and quality of life scores.
Semaglutide did cause more adverse effects and lead to a higher rate of study discontinuation compared to control. Side effects were characteristic of the GLP-1 receptor agonist class profile and included serious gastrointestinal (1.4% vs 0% in placebo) and gallbladder (2.6% vs 1.2% in placebo) disorders. Overall, 7% of semaglutide patients and 3.1% of placebo patients discontinued therapy due to adverse events. No treatment-related deaths were reported in either group.
This well-designed study reports convincing data for the use of high-dose semaglutide in obese patients without diabetes. The study population was overwhelmingly female (~75%) and white (~75%) with an average age of 46-47 years old which may limit its generalizability. In this trial, weight loss reached a maximum at week 60 in the treatment group, but it is not yet known if weight loss is maintained with or without treatment after 68 weeks. A subset of patients in this trial are being followed for up to 2.5 years, which may offer insight into the long-term benefits of semaglutide for weight loss.
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Wilding John PH, Batterham Rachel L, Calanna Salvatore, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. NEJM 2021. DOI: 10.1056/NEJMoa2032183
Ingelfinger Julie R and Clifford J Rosen. STEP 1 for Effective Weight Control – Another First Step? NEJM 2021. DOI: 10.1056/NEJMe2101705.