Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
Once-Weekly Semaglutide in Overweight or Obese Adults
TAKE-HOME MESSAGE
-
This double-blind trial randomized 1961 individuals with overweight or obesity in a 2:1 ratio to 68 weeks of once-weekly 2.4 mg subcutaneous semaglutide versus placebo plus lifestyle intervention. The semaglutide group had a mean change in body weight of −14.9% from baseline compared with −2.4% in the placebo group. Participants achieving weight reductions of 5% or more, 10% or more, and 15% or more were significantly higher in the semaglutide group. Cardiometabolic risk factors also were improved to a greater extent in the semaglutide group.
- Semaglutide 2.4 mg weekly in individuals who are overweight or obese, in addition to lifestyle intervention, led to significant, clinically relevant weight reduction.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.
METHODS
In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.
RESULTS
The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).
CONCLUSIONS
In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
Additional Info
Disclosure statements are available on the authors' profiles:
Once-Weekly Semaglutide in Adults with Overweight or Obesity
N. Engl. J. Med 2021 Feb 10;[EPub Ahead of Print], JPH Wilding, RL Batterham, S Calanna, M Davies, LF Van Gaal, I Lingvay, BM McGowan, J Rosenstock, MTD Tran, TA Wadden, S Wharton, K Yokote, N Zeuthen, RF KushnerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Diabetes
In this double-blind study, 1961 persons with obesity (BMI ≥30 kg/m2 or ≥27 kg/m2 plus at least one obesity comorbidity) were randomized 2:1 to once-weekly semaglutide 2.4 mg or placebo, both in addition to therapeutic lifestyle changes, for 68 weeks. The mean change in weight was −15.3 kg (−14.9%) with semaglutide compared with −2.6 kg (−2.4%) with placebo (P < .0001), and more participants in the semaglutide arm lost ≥5% of body weight (86.4% vs 31.5%; P < .001). Significant improvements in patient-reported outcomes such as physical functioning and metabolic and cardiovascular risk factors were observed with semaglutide versus placebo. Although overall adverse events (89.7% vs 86.4%) were similar, severe adverse events (9.8% vs 6.4%) and treatment discontinuation (7.0% vs 3.1%) were more common with semaglutide, a difference that was attributed primarily to gastrointestinal events.
In this study, weight loss exceeded that reported with other currently approved weight-loss medications, including liraglutide.1 However, studies comparing semaglutide with active pharmacologic comparators or bariatric surgery and in populations that include greater representation of minority groups would be useful for confirming these findings. In addition, longer-term studies are needed to appreciate the durability of weight loss. In summary, once-weekly subcutaneous semaglutide demonstrated clinically meaningful weight loss, supporting its use for treatment of obesity.
Reference