Obesity is treated as a chronic disease: STEP-4 showed weight regain after stopping semaglutide. STEP-1 (14.9% mean weight loss at 68 weeks) and SURMOUNT-1 (20.9% at 72 weeks on 15 mg) are the foundational trials.
The evidence
STEP-1 (NEJM 2021): 14.9% mean weight loss with semaglutide 2.4 mg vs 2.4% placebo at 68 weeks. SURMOUNT-1 (NEJM 2022): 20.9% mean weight loss with tirzepatide 15 mg vs 3.1% placebo at 72 weeks (treatment-regimen estimand). SURMOUNT-5 (NEJM 2025): 20.2% with tirzepatide vs 13.7% with semaglutide. STEP-4 (JAMA 2021): weight regain after discontinuation establishes the chronic-disease model.
FDA-approved labeling status
Wegovy (semaglutide 2.4 mg) FDA-approved 2021 for chronic weight management; pediatric 12+ 2022. Zepbound (tirzepatide) FDA-approved November 2023. Foundayo (orforglipron) tablets FDA-approved April 1, 2026 and the Wegovy pill in December 2025. All are for adults with obesity, or overweight with at least one weight-related condition (BMI 30 or more, or 27 or more with a condition, in the trials).
Practical considerations
BMI eligibility, lifestyle pairing (protein + resistance training for muscle preservation), and long-term therapy expectations are all clinically meaningful. See our muscle preservation guide and maintenance & discontinuation guide.