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

Zusammenfassung

Semaglutide 2.4 mg, as adjunct to lifestyle intervention, was efficacious for weight management in adults with overweight or obesity and T2D, providing significantly greater weight loss vs. placebo and semaglutide 1.0 mg at week 68.

Einleitung

In people with overweight/obesity and type 2 diabetes (T2D), achievement of weight loss can be a challenge. STEP 2 investigated the efficacy and safety of semaglutide 2.4 mg for weight management in adults with overweight/obesity and T2D.

Material und Methodik

This randomized, double-blind, placebo-controlled, phase 3 trial was conducted across 12 countries. Adults with body mass index (BMI)≥27 kg/m2, T2D, HbA1c between 7–10% (53–86 mmol/mol), and receiving≤3 oral glucose-lowering agents were randomized 1:1:1 to once-weekly subcutaneous (s.c.) semaglutide 2.4 mg or 1.0 mg, or placebo, as adjunct to a reduced-calorie diet and increased physical activity for 68 weeks. The co-primary endpoints were percentage change in body weight and proportion of participants achieving weight loss≥5% for semaglutide 2.4 mg vs. placebo.Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise.

Ergebnisse

1,210 participants (mean: age 55 years, body weight 99.8 kg, BMI 35.7 kg/m2, HbA1c 8.1%, diabetes duration 8.0 years; 50.9% female) were randomized. Mean body weight change from baseline to week 68 was−9.6% with semaglutide 2.4 mg vs.−3.4% with placebo (estimated treatment difference [ETD]:−6.2%; 95% confidence interval [CI]:−7.3,−5.2; p<0.0001) and−7.0% for semaglutide 1.0 mg (ETD for semaglutide 2.4 mg vs. 1.0 mg: − 2.7%; 95% CI:−3.7,−1.6; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change−10.6% for semaglutide 2.4 mg vs.−3.1% for placebo (ETD:−7.6%; 95% CI:−8.6,−6.6; p<0.0001) and 7.6% for semaglutide 1.0 mg (ETD vs. semaglutide 2.4 mg:−3.1%; 95% CI:−4.1, − 2.1; p<0.0001). Participants on semaglutide 2.4 mg were more likely to achieve weight loss≥5%,≥10%, and≥20% vs. placebo (68.8% vs. 28.5%, 45.6% vs. 8.2%, and 13.1% vs. 1.6%, respectively; p value for odds ratios < 0.0001 for all). Mean change in HbA1c from baseline to week 68 was−1.6% for semaglutide 2.4 mg vs.−0.4% for placebo (p<0.0001).The most frequent adverse events were gastrointestinal disorders (typically transient ), occurring in 57.5%, 63.5% and 34.3% of participants receiving semaglutide 1.0 mg, 2.4 mg and placebo, respectively.

Publication History

Article published online:
24 September 2021