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.

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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