This meta-analysis aimed to assess the efficacy and safety of once-weekly semaglutide among adults with overweight or obesity.We searched multiple electronic databases for randomized controlled trials that compared once-weekly semaglutide versus placebo in adults with overweight or obesity. The primary outcomes were the percentage change and absolute change in body weight. Secondary outcomes included achievement of categorical weight loss targets (at least 5, 10, 15, or 20%), cardiometabolic risk profiles, and health-related quality of life.This meta-analysis included a total of four trials with 3447 patients. Once-weekly semaglutide was superior to placebo in terms of the percentage change and absolute change in body weight. Compared with placebo, once-weekly semaglutide also led to significant increases in the proportions of achievement of categorical weight reduction targets. Moreover, once-weekly semaglutide induced superior reductions in waist circumference and body-mass index compared with placebo. Furthermore, the effect on improving other cardiometabolic risk factors and health-related quality of life was more pronounced for once-weekly semaglutide relative to placebo.Among adults with overweight or obesity, once-weekly semaglutide could result in clinically meaningful weight loss, which was a promising therapy for treating overweight or obesity.© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.