Journal Article

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

Jódar, Esteban, Garvey, W Timothy, Batterham, Rachel L, Wharton, Sean, Frias, Juan P, Christensen, Louise N, Bhatta, Meena, Rigas, Georgia, Wadden, Thomas A, Buscemi, Silvio, Kandler, Kristian

2022

Overview

The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg m and weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was -15.2% in the semaglutide group (n = 152) versus -2.6% with placebo (n = 152), for an estimated treatment difference of -12.6 %-points (95% confidence interval, -15.3 to -9.8; P < 0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430.

• Publisher: Nature Publishing Group,Nature Publishing Group US
• Subject: Adult / Adults / Antidiabetics / Body mass / Body mass index / Body size / Body weight / Body weight loss / Comorbidity / Diabetes mellitus / Diabetes Mellitus, Type 2 - drug therapy / Double-Blind Method / Effectiveness / Female / Glucagon-Like Peptides / Humans / Hypoglycemic Agents - adverse effects / Male / Middle Aged / Obesity / Obesity - complications / Obesity - drug therapy / Overweight / Overweight - complications / Overweight - drug therapy / Placebos / Safety / Treatment Outcome / Weight control / Weight Loss