Semaglutide (Ozempic/Wegovy) vs tirzepatide (Mounjaro/Zepbound) — a head-to-head breakdown of efficacy, side effects, mechanism, cost, and who should consider each drug.
| Feature | Semaglutide | Tirzepatide |
|---|---|---|
| Drug class | GLP-1 receptor agonist | Dual GIP/GLP-1 receptor agonist |
| Receptors activated | GLP-1 only | GLP-1 + GIP |
| Appetite suppression | Strong | Stronger (dual pathway) |
| Gastric emptying slowing | Yes | Yes |
| GI side effect profile | Higher nausea | Lower nausea (GIP offsets) |
| Drug / Dose | Avg Weight Loss | % Losing ≥20% | Trial |
|---|---|---|---|
| Semaglutide 1mg (Ozempic) | ~6–7% BW | <5% | SUSTAIN |
| Semaglutide 2.4mg (Wegovy) | 14.9–15.5% BW | 28–32% | STEP / SURMOUNT-5 |
| Tirzepatide 10mg (Zepbound) | 20.9% BW | 45% | SURMOUNT-1 |
| Tirzepatide 15mg (Zepbound) | 22.5% BW | 57% | SURMOUNT-1 |
🏆 Tirzepatide wins on efficacy by a significant margin. The SURMOUNT-5 head-to-head trial (2024) confirmed tirzepatide produces approximately 47% more weight loss than semaglutide at maximum approved doses.
| Metric | Semaglutide (best dose) | Tirzepatide (best dose) |
|---|---|---|
| A1c reduction | Up to −2.0% | Up to −2.58% |
| Fasting glucose reduction | ~40 mg/dL | ~55 mg/dL |
| CV event reduction | 20% (SELECT trial, Wegovy) | Data pending (SURPASS-CVOT) |
| Kidney protection | Yes (FLOW trial, Ozempic) | Data emerging |
⚠️ Semaglutide currently has stronger evidence for cardiovascular and kidney protection. If you have established heart disease or diabetic kidney disease, your cardiologist or nephrologist may prefer semaglutide.
| Side Effect | Semaglutide 2.4mg | Tirzepatide 15mg |
|---|---|---|
| Nausea | ~44% | ~25–30% |
| Vomiting | ~24% | ~10–15% |
| Diarrhea | ~30% | ~20–25% |
| Constipation | ~24% | ~15–20% |
| Discontinuation (GI) | ~7% | ~5% |
Tirzepatide is generally better tolerated. Researchers attribute this partly to GIP's ability to counteract GLP-1-induced nausea at the level of the brainstem.
| Drug | Brand | List Price/Month | Self-Pay Options |
|---|---|---|---|
| Semaglutide 0.5–2mg | Ozempic | ~$935 | GoodRx ~$880 |
| Semaglutide 2.4mg | Wegovy | ~$1,349 | Limited |
| Tirzepatide 2.5–15mg | Mounjaro / Zepbound | ~$1,060 | LillyDirect vials $349–$549 |
💡 The LillyDirect self-pay vial program makes Zepbound/Mounjaro the most affordable brand-name option for self-pay patients at $349–$549/month vs $935+ for Ozempic.
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