Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist primarily used to improve glycemic control in adults with type 2 diabetes. Its use is associated with improved cardiovascular and renal outcomes and reduced all-cause mortality. One favorable side effect of semaglutide is weight loss, and researchers have now studied its use in adults with overweight or obesity and without diabetes.
A total of 1961 adults (74% female, mean age 46) with at least 1 failed attempt at weight loss through diet and either BMI ≥30 or ≥27 with 1 comorbidity, were randomized in a 2:1 ratio to weekly subcutaneous injections of semaglutide or placebo for 68 weeks. Semaglutide dosing was started at 0.25 mg for the first 4 weeks and increased at 4-week intervals up to 2.4 mg. Both groups received monthly counseling that encouraged a reduced-calorie diet and 150 minutes of weekly physical activity. The coprimary endpoints were percentage change in body weight and reduction of body weight of 5% or more from baseline to week 68.
The mean body weight reduction from baseline to 68 weeks was 14.9.% with semaglutide vs 2.4% with placebo (P <.001). Participants who received semaglutide were more likely to lose ≥10% and ≥15% of baseline body weight (P <.001, with number needed to treat of 2 and 3 respectively). The most common side effects of semaglutide were nausea and diarrhea but the overall dropout rate was low and adherence to treatment was high.
It is worth noting that the price tag for semaglutide is high. A 1-month supply of semaglutide is about $900, which makes the cost of 68 weeks of treatment around $13,000. This cost is similar to surgical weight loss interventions, which have varying degrees of sustained weight loss, something not currently known with semaglutide. Nonetheless, semaglutide may be a suitable option as an adjunct to diet and exercise for weight loss.
Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Massachusetts, and assistant clinical professor in family medicine, University of Massachusetts Medical School, Worcester.
DynaMed is a database that provides evidence-based information on more than 3000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.
Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight and obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183