Retatrutide vs Tirzepatide
A neutral, side-by-side comparison of two glp-1 & metabolic peptides — their mechanisms, dosing ranges, administration routes, side effects, and research evidence. For research and educational purposes only.
Retatrutide
Retatrutide (LY3437943) is Eli Lilly's investigational once-weekly triple agonist of the GIP, GLP-1, and glucagon receptors. Phase 2 data showed 24.2% mean weight loss at 48 weeks; the Phase 3 TRIUMPH program has since reported topline weight loss approaching 28–30% — among the largest reductions recorded for any obesity pharmacotherapy. It is not yet FDA-approved.
Full profileTirzepatide
Tirzepatide is a dual GIP/GLP-1 receptor agonist — the first in its class to activate both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors simultaneously. Approved as Mounjaro (type 2 diabetes) and Zepbound (obesity), it produces greater weight loss than any approved GLP-1 monotherapy in clinical trials.
Full profile| Retatrutide | Tirzepatide | |
|---|---|---|
| Category | GLP-1 & Metabolic | GLP-1 & Metabolic |
| Also known as | LY3437943, Triple G, GIP/GLP-1/Glucagon Receptor Agonist | LY3298176, Mounjaro, Zepbound |
| Evidence | Investigational (in trials) | FDA-approved |
| Dosing range | 2mg–12mg mg, once weekly | 2.5mg–15mg mg, Once weekly subcutaneous injection |
| Administration | Subcutaneous injection (weekly) | Subcutaneous injection (abdomen, thigh, or upper arm) |
| Key side effects | Nausea (most common, dose-dependent), Vomiting, Diarrhea, Constipation | Nausea (most common, especially during titration), Vomiting, Diarrhea, Constipation |
| Cited sources | 6 references | 4 references |
Key differences
- Evidence level differs: Retatrutide is investigational (in trials), while Tirzepatide is fda-approved.
- Administration: Retatrutide — Subcutaneous injection (weekly); Tirzepatide — Subcutaneous injection (abdomen, thigh, or upper arm).
- Frequency: Retatrutide is typically once weekly; Tirzepatide is Once weekly subcutaneous injection.
- Research depth: this profile cites 6 sources for Retatrutide vs 4 for Tirzepatide.
How each works
Retatrutide
Across the Phase 2 trial (NEJM 2023, Jastreboff et al.) and the Phase 3 TRIUMPH registrational program (TRIUMPH-1 through -4), retatrutide has produced dose-dependent weight loss reaching ~28.3% at 80 weeks (TRIUMPH-1, 12 mg) and ~28.7% at 68 weeks in a knee-osteoarthritis population (TRIUMPH-4, 12 mg), alongside improvements in glycemia, blood pressure, lipids, and liver fat. The glucagon component is thought to add energy expenditure on top of the appetite suppression driven by GLP-1 and GIP. As of mid-2026, Phase 3 efficacy figures are topline (press-release/conference level) and not yet published in full peer-reviewed form.
Tirzepatide
The SURMOUNT-1 trial (N=2539) demonstrated up to 22.5% mean body weight reduction over 72 weeks at the 15mg dose — the highest efficacy ever recorded for a pharmaceutical weight loss agent at time of publication. The dual mechanism leverages GIP's potentiation of insulin secretion and adipose tissue effects alongside GLP-1's appetite suppression and gastric motility slowing. Head-to-head data (SURMOUNT-5) shows tirzepatide outperforms semaglutide 2.4mg for weight loss.
This comparison aggregates public research and structured profile data for informational purposes only. It is not medical advice and does not recommend either compound for human use. Consult a qualified healthcare provider before considering any peptide.