Adults with obesity treated with semaglutide 2.4 mg achieved and maintained a significant amount of weight loss in a 68-week trial.-Novo Nordisk

New results from the STEP phase IIIa clinical trial programme demonstrated weight loss with investigational treatment of once-weekly subcutaneous semaglutide 2.4 mg versus placebo. In the STEP 4 trial, study participants who reached the maintenance dose of semaglutide 2.4 mg during a 20-week run-in period were randomised to either continue treatment with semaglutide 2.4 mg or switch to placebo for 48 weeks. The full results of the STEP 4 trial were presented at the virtual Endocrine Society (ENDO) 2021 Annual Meeting and published in the Journal of the American Medical Association. Following the 20-week run-in period, people who continued treatment with semaglutide 2.4 mg for an additional 48 weeks continued to lose weight with a statistically significant additional mean weight loss of 7.9% , (8.8% for the trial product estimand from week 20 to week 68. People who were switched to placebo following the 20-week run-in period regained 6.9% of their body weight from week 20 to 68 (6.5% for the trial product estimand ). The estimated treatment difference [ETD] for the treatment policy estimand was -14.8% (95% confidence interval [CI]: -16.0, -13.5; p<0.0001). people who stayed on semaglutide 2.4 mg throughout the entire 68-week trial achieved a total weight loss of 17.4% (18.2% for the trial product estimand ). both treatment groups followed a reduced-calorie diet and increased physical activity programme throughout the study. the semaglutide 2.4 mg safety profile is in line with observations seen previously with glp-1 receptor agonists. it is generally well-tolerated, and the most common adverse events among people treated with semaglutide 2.4 mg were gastrointestinal events. about step 4 and the step clinical trial programme : step 4 was a 68-week phase iiia randomised, double-blind, multicentre, placebo-controlled trial that compared the safety and efficacy of once-weekly subcutaneous semaglutide 2.4 mg versus placebo on change in body weight. the trial was designed to assess the effect of continuing versus discontinuing semaglutide 2.4 mg in adults with obesity (bmi 30 kg m2), or overweight (bmi 27 kg m2) with at least one weight-related comorbidity and without type 2 diabetes (hba1c><6.5%). during the 20-week run-in period (week 0 to week 20), participants were treated with semaglutide (16 weeks escalation, followed by 4 weeks at the target dose) as an adjunct to lifestyle intervention (–500 kcal day diet together with 150 minutes week of physical activity). following the run-in period, the 803 people who reached the maintenance dose of semaglutide (2.4 mg) reduced their mean body weight from 107.2 kg (week 0) to 96.1 kg (week 20) and were randomised (in a 2:1 ratio) to continue treatment with semaglutide 2.4 mg or switch to placebo for a further 48 weeks (week 20 to week 68) with lifestyle intervention. the primary endpoint of the trial was the percentage change in body weight from randomisation (week 20) to the end of treatment (week 68). confirmatory secondary endpoints included change in waist circumference, systolic blood pressure, and physical functioning score on the 36-item short form survey (sf-36), assessed from randomisation (week 20) to the end of treatment (week 68). supportive secondary endpoints included percent change in body weight from baseline (week 0) to the end of treatment (week 68). step (semaglutide treatment effect in people with obesity) is a phase iii clinical development programme with once-weekly subcutaneous semaglutide 2.4 mg in obesity. the global clinical phase |iiia programme consists of four trials and has enrolled approximately 4,500 adults with overweight or obesity. see- "effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity-the step 4 randomized clinical trial"- domenica rubino, md; niclas abrahamsson, md; melanie davies, md,; et al for the step 4 investigators.jama. published online march 23, 2021. doi:10.1001 jama.2021.3224.>