Tirzepatide vs semaglutide: what the trials actually show
The two dominant GLP-1 weight-loss drugs compared on efficacy, side effects, cost, and dosing — with the primary-source trial data cited inline.
Tirzepatide and semaglutide are the two most prescribed GLP-1 receptor agonists for weight management. Both are FDA approved. They differ in receptor mechanism (dual GIP/GLP-1 vs GLP-1 only), in average weight loss at equivalent trial durations, and in side-effect profile. Below is the head-to-head as of April 2026.
| Field | Tirzepatide | Semaglutide |
|---|---|---|
| Brand names | Mounjaro, Zepbound | Ozempic, Wegovy, Rybelsus |
| Manufacturer | Eli Lilly | Novo Nordisk |
| FDA approved | 2022 (T2D), 2023 (obesity) | 2017 (T2D), 2021 (obesity) |
| Indication | Type 2 diabetes + chronic weight management | Type 2 diabetes + chronic weight management |
| Mechanism | Dual GIP / GLP-1 receptor agonist | GLP-1 receptor agonist (single pathway) |
| Delivery | Once-weekly subcutaneous injection | Once-weekly subcutaneous injection (Rybelsus: daily oral) |
| Avg weight loss | ~20.9% at 72 weeks (SURMOUNT-1, 15 mg) | ~14.9% at 68 weeks (STEP-1, 2.4 mg) |
Primary sources
- Tirzepatide: SURMOUNT-1 (NEJM, 2022)
- Semaglutide: STEP-1 (NEJM, 2021)
Frequently asked
Is tirzepatide really more effective than semaglutide?
For average weight loss at peak dose, yes — Phase 3 trial data shows tirzepatide 15 mg producing ~20.9% body-weight reduction at 72 weeks vs semaglutide 2.4 mg producing ~14.9% at 68 weeks. Head-to-head trials (SURMOUNT-5, reported May 2025) confirm tirzepatide's efficacy edge directly. Individual response varies.
Which one has worse side effects?
Side-effect profiles are broadly similar — nausea, diarrhea, constipation, vomiting — and are dose-dependent for both. Discontinuation rates due to side effects in Phase 3 trials are comparable (roughly 4-7% for both). No categorical difference.
Are these drugs still being compounded in 2026?
No, not legally in most cases. The FDA declared the semaglutide shortage resolved February 2025 and the tirzepatide shortage resolved December 2024; 503A and 503B compounding pharmacies lost discretion shortly after. See our FDA tracker for current status.
What about cost?
Both list at ~$1,000-1,300 per month without insurance. Manufacturer savings programs (LillyDirect for Zepbound, NovoCare for Wegovy) can reduce cost for eligible patients. Insurance coverage for obesity (not diabetes) remains inconsistent.