Once-Weekly Semaglutide in Adults with Overweight or Obesity

作者：John P.H. Wilding, Rachel Louise Batterham, Salvatore Calanna, Melanie J. Davies, Luc F. Van Gaal, Ildiko Lingvay, Barbara M. McGowan, Julio Rosenstock, Marie Thi Dao Tran, Thomas A. Wadden, Sean Wharton, Koutaro Yokote, Niels Zeuthen, Robert F. Kushner · 发表于：New England Journal of Medicine · 年份：2021 · DOI：10.1056/nejmoa2032183 · 被引用次数：5043 · 研究领域：Diabetes Treatment and Management、Metabolism, Diabetes, and Cancer、Bariatric Surgery and Outcomes

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...