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Once-Weekly Semaglutide in Adults with Overweight or Obesity
STEP 1 randomized 1,961 adults with overweight/obesity without diabetes to once-weekly semaglutide 2.4 mg versus placebo for 68 weeks on a lifestyle background: large mean body-weight reductions and high proportions achieving ≥5%, ≥10%, and ≥15% loss versus placebo.
Design
- Double-blind trial; n = 1,961 (1,306 semaglutide 2.4 mg weekly vs 655 placebo), 68 weeks, plus lifestyle intervention in both arms
- Entry: BMI ≥30, or ≥27 with ≥1 weight-related comorbidity; excluded diabetes
- Coprimary estimands: % change in body weight and proportion achieving ≥5% weight loss (primary estimand handles treatment discontinuation/rescue per protocol)
Key efficacy outcomes (ITT primary estimand summary)
- Mean % weight change: −14.9% (semaglutide) vs −2.4% (placebo); estimated difference −12.4 percentage points (95% CI −13.4 to −11.5; P < 0.001)
- Responder thresholds (week 68): ≥5% loss: 86.4% vs 31.5%; ≥10%: 69.1% vs 12.0%; ≥15%: 50.5% vs 4.9% (P < 0.001 for odds comparisons)
- Mean weight change: −15.3 kg vs −2.6 kg; estimated difference −12.7 kg (95% CI −13.7 to −11.7)
Safety / adherence (headline)
- GI adverse events were the dominant class; discontinuations higher on semaglutide—read AE tables before extrapolating to community tolerability.
Publication
Wilding JPH, Batterham RL, Calanna S, et al. N Engl J Med. 2021 Mar 18;384(11):989–1002. PMID 33567185.
Outcomes
- Mean body-weight change −14.9% with semaglutide 2.4 mg weekly vs −2.4% with placebo at week 68 (estimated difference −12.4 percentage points; 95% CI −13.4 to −11.5; P<0.001).
- ≥5% weight loss at week 68: 86.4% (1047/1211) on semaglutide vs 31.5% (182/579) on placebo; ≥10%: 69.1% vs 12.0%; ≥15%: 50.5% vs 4.9% (all P<0.001 for odds vs placebo).