GLP-1s for Obesity
GLP-1 and dual GLP-1/GIP therapies are the most effective approved pharmacotherapies for chronic weight management, with mean total body weight loss of 15–22.5% over 68–88 weeks.
Effect sizes
In STEP-1, semaglutide 2.4 mg produced mean weight loss of 14.9% over 68 weeks vs 2.4% with placebo. In SURMOUNT-1, tirzepatide 15 mg produced 22.5% mean weight loss over 72 weeks vs 2.4% with placebo — the largest effect ever observed in a non-surgical obesity trial. Roughly 40% of tirzepatide-treated participants lost at least 25% of baseline body weight.
Maintenance
STEP-4 (semaglutide) and SURMOUNT-4 (tirzepatide) demonstrated that withdrawal of therapy is followed by partial weight regain over 1–2 years. The clinical implication is that, like other chronic-disease medications, GLP-1 therapy for obesity is typically long-term — not a short course.
Who qualifies under labeling
FDA labeling for Wegovy and Zepbound covers adults with BMI ≥ 30, or BMI ≥ 27 with at least one weight-related comorbidity (hypertension, dyslipidemia, T2D, OSA). Pediatric labeling exists for adolescents 12+ for both drugs.
Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Pregnancy and breastfeeding
- Severe gastrointestinal disease (relative)