Established semaglutide 2.4 mg as chronic weight management therapy.
STEP-1 — foundational
Wilding et al. (NEJM 2021): 1,961 adults BMI ≥30 (or ≥27 + comorbidity), no diabetes. Sema 2.4 mg vs placebo + lifestyle. Mean weight loss 14.9% (sema) vs 2.4% (placebo) at 68 weeks. 32% lost ≥20% body weight. Basis for Wegovy approval (June 2021).
STEP-4 — discontinuation
Rubino et al. (JAMA 2021): tested discontinuation after 20-week titration. Continuation arm: additional loss to ~17%. Withdrawal arm: ~7% regain. Established obesity as chronic disease requiring chronic therapy.
STEP-HFpEF
Kosiborod et al. (NEJM 2023): 529 adults with HFpEF + obesity. Semaglutide improved KCCQ-CSS symptom score by 7.8 points more than placebo at 52 weeks. Improved 6-minute walk distance. Direct cardiac effects beyond weight loss.
Implications
- 14–17% weight loss realistic at full dose with adherence
- Long-term therapy default
- Cardiometabolic benefits accompany weight loss