Once-Weekly Semaglutide in Adults with Overweight or Obesity

Author: Wilding, John P. H.; Batterham, Rachel L.; Calanna, Salvatore; Davies, Melanie; Van Gaal, Luc F.; Lingvay, Ildiko; McGowan, Barbara M.; Rosenstock, Julio; Tran, Marie T. D.; Wadden, Thomas A.; Wharton, Sean; Yokote, Koutaro; Zeuthen, Niels; Kushner, Robert F.; STEP 1 Study Group

Description: BACKGROUND: 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.

Subject headings: Semaglutide; Obesity; Overweight; Weight loss; Lifestyle intervention

Publication year: 2021

Journal or book title: The New England Journal of Medicine

Volume: 384

Pages: 989-1002

Find the full text: https://www.gwern.net/docs/longevity/2021-wilding.pdf

Find more like this one (cited by): https://scholar.google.com/scholar?cites=5620455396962236113&as_sdt=5,26&sciodt=0,26&hl=en

Serial number: 3276

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