Two-year Effect of Semaglutide 2.4 mg vs Placebo in Adults with Overweight or Obesity: STEP 5

• Published in: Obesity (Silver Spring, Md.) Md.), 2021-12, Vol.29, p.43-43
• Main Authors: Garvey, W Timothy, Batterham, Rachel, Bhatta, Meena, Buscemi, Silvio, Christensen, Louise, Frias, Juan, Jodar, Esteban, Kandler, Kristian, Rigas, Georgia MBBS FRACGP, Wadden, Thomas, Wharton, Sean
• Format: Article
• Language: English
• Subjects: Antidiabetics; Body mass index; Obesity; Overweight; Risk factors; Weight control
• ISSN: 1930-7381; 1930-739X

Background: The 2-year efficacy and safety of once-weekly (OW) subcutaneous semaglutide 2.4 mg vs placebo in adults with overweight/obesity was assessed in the STEP 5 phase 3 trial (NCT03693430). Methods: STEP 5 was a randomized, double-blind, placebo-controlled trial in 5 countries. Adults with body mass index (BMI) >30 kg/m2, or >27 kg/m2 with >1 weight-related comorbidity, without diabetes, were randomized 1:1 to 104 weeks' treatment with semaglutide 2.4 mg or placebo. The co-primary endpoints were percent change in body weight (BW) and achievement of weight loss >5%. Cardiometabolic risk factors and safety/tolerability were also assessed. Data shown are for the treatment policy estimand (assesses effects regardless of treatment adherence and use of other anti-obesity therapies). P values for parameters marked with # were not controlled for multiplicity. Results: In total, 304 adults were randomized (78% female; 93% white; mean age 47 years, BW 106.0 kg, and BMI 38.5 kg/m2). Mean BW change from baseline to week 104 was -15.2% with semaglutide vs -2.6% with placebo (estimated treatment difference: -12.6 %-points; 95% confidence interval: -15.3, -9.8; p < 0.0001). Participants were more likely to lose >5%, >10%, >15%, and >20%# BW with semaglutide vs placebo (77.1% vs 34.4%, 61.8% vs 13.3%, 52.1% vs 7.0%, and 36.1% vs 2.3%, respectively; p < 0.0001 for all odds ratios). Greater improvements were seen with semaglutide vs placebo in waist circumference, BMI#, systolic and diastolic# blood pressure, HbA1c#, fasting plasma glucose#, fasting serum insulin#, C-reactive protein#, and lipids# (total cholesterol, VLDL cholesterol, and triglycerides) (p < 0.05 for all). No new safety signals with semaglutide were observed. Conclusions: Subcutaneous semaglutide 2.4 mg OW for 2 years resulted in substantial and sustained BW reductions and improvements in cardiometabolic risk factors vs placebo, indicating a favorable benefit-risk profile of semaglutide 2.4 mg for long-term management of weight and cardiometabolic risk factors.