2 Efficacy and Safety of Once-Weekly Subcutaneous Semaglutide 2.4 mg in Adults With Overweight or Obesity (STEP 1)

Zusammenfassung

In adults with overweight or obesity, once-weekly s.c. semaglutide 2.4 mg plus lifestyle intervention induced a mean weight loss of approximately 15% by week 68. Clinically beneficial weight loss of≥10% was achieved by over two-thirds of participants.

Einleitung

Despite the increasing adverse health impact of obesity, there are few pharmacological options for effective weight management. STEP 1 investigated the efficacy and safety of the glucagon-like peptide-1 analogue, subcutaneous (s.c.) semaglutide 2.4 mg, for weight management in adults with overweight or obesity.

Material und Methodik

This randomised, double-blind, placebo-controlled, phase 3 trial was conducted across 16 countries. Adults aged≥18 years with either body mass index (BMI)≥30 kg/m², or BMI≥27 kg/m² with≥1 weight-related comorbidity, without type 2 diabetes, were randomised to 68 weeks’ treatment with once-weekly s.c. semaglutide 2.4 mg or placebo, both as adjunct to lifestyle intervention. The co-primary endpoints were percentage change in body weight and achievement of weight loss≥5%. Two estimands were defined: treatment policy (effect regardless of treatment adherence and use of rescue intervention) and trial product (effect assuming treatment adherence and without rescue intervention); results are presented for the treatment policy estimand unless stated otherwise. P values for parameters marked # were not controlled for multiplicity.

Ergebnisse

1961 randomised participants (mean age 46 years, body weight 105.3 kg, BMI 37.9 kg/m²; 74.1% female) were included. Mean body weight change from baseline to week 68 was−14.9% in the semaglutide group vs.−2.4% with placebo (estimated treatment difference [ETD]:−12.4%; 95% confidence interval (CI):−13.4,−11.5; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change# was –16.9% for semaglutide vs. –2.4% for placebo (ETD: –14.4%; 95% CI: –15.3, –13.6; p<0.0001). Participants were more likely to achieve weight loss≥5%,≥10%, and≥20%# with semaglutide vs. placebo (86.4% vs. 31.5%, 69.1% vs. 12.0%, and 32.0% vs. 1.7%, respectively; p<0.0001 for all). Greater improvements were seen with semaglutide vs. placebo in waist circumference, systolic and diastolic# blood pressure, and self-reported physical functioning (p<0.05 for all). No new safety signals with semaglutide were observed.

Publication History

Article published online:
24 September 2021