Obesity is treated as a chronic disease — the framing established by STEP-4 (semaglutide), which showed weight regain after discontinuation. Long-term therapy is the default expectation. STEP-1 (sema, ~14.9% mean weight loss at 68 weeks) and SURMOUNT-1 (tirz, up to 22.5% at 72 weeks) 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% weight loss with tirzepatide 15 mg at 72 weeks. 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. Both for BMI ≥30 or BMI ≥27 with comorbidity.
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.