Retatrutide vs Tirzepatide: Which Is Right for Your Protocol?
A triple vs dual agonist comparison — mechanism, dosing, trial results, side effects, and cost — for research purposes.
Mechanism
Retatrutide is a triple agonist (GLP-1 + GIP + glucagon). Tirzepatide is a dual agonist (GLP-1 + GIP). The extra glucagon target is what sets retatrutide apart.
Weight-loss data
Retatrutide Phase 3: up to 28.7% at 68 weeks (TRIUMPH-4, reported December 2025). Tirzepatide Phase 3: ~22.5% at 72 weeks. Retatrutide edges ahead but has no direct head-to-head trial.
Dosing complexity
Tirzepatide has the simpler, FDA-established titration path. Retatrutide requires a longer, more cautious titration due to the glucagon component.
Cost & availability
Tirzepatide is FDA-approved (Mounjaro, Zepbound) and cheaper per mg on the research market. Retatrutide is research-only, priced ~25–40% higher per mg.
Side-by-Side Comparison
Retatrutide vs Tirzepatide at a Glance
| Parameter | Retatrutide | Tirzepatide |
|---|---|---|
| Mechanism | Triple agonist | Dual agonist |
| Receptors targeted | GLP-1 + GIP + Glucagon | GLP-1 + GIP |
| Typical weekly dose range | 2–12 mg | 2.5–15 mg |
| Titration schedule | 6 steps over ~20+ weeks | 6 steps over ~20+ weeks |
| Half-life | ~6 days | ~5 days |
| Trial data summary | Phase 3: up to 28.7% at 68 wks (TRIUMPH-4, reported Dec 2025) | Phase 3: ~22.5% at 72 wks (15 mg) |
| Common side effects | Nausea, vomiting, fatigue, elevated HR | Nausea, vomiting, constipation |
| Approx. cost per 10 mg vial | $80–$120 | $60–$100 |
| FDA approval | Not approved (Phase 3) | Approved (Mounjaro, Zepbound) |
Mechanism: Triple vs Dual Agonist
Retatrutide is a triple agonist that acts on the GLP-1, GIP, and glucagon receptors. The GLP-1 and GIP components drive appetite suppression, slowed gastric emptying, and glucose-dependent insulin secretion — the same mechanisms behind tirzepatide. The added glucagon receptor agonism is proposed to increase energy expenditure, meaning retatrutide is theorized to influence both energy intake and output simultaneously. Retatrutide is in Phase 3 trials and is not FDA-approved.
Tirzepatide is a dual GIP and GLP-1 receptor agonist. It was the first approved dual incretin receptor agonist and is FDA-approved as Mounjaro (type 2 diabetes) and Zepbound (weight management). GIP receptor activation is proposed to enhance insulin sensitivity and may improve tolerability compared to GLP-1 alone. This section describes general pharmacology and is not medical guidance.
Dosing & Reconstitution
How the Two Compare in Practice
Retatrutide
Start at 2 mg weekly for 4 weeks, then advance in 2 mg increments every 4 weeks to a target of 4–12 mg. Reconstitute at 10.0 mg/mL for doses of 4 mg and above to keep injection volume manageable.
Calculate Retatrutide Dose →Tirzepatide
Start at 2.5 mg weekly for 4 weeks, then advance in 2.5 mg increments every 4 weeks to a target of 5–15 mg. Reconstitute at 5.0–10.0 mg/mL; 10.0 mg/mL keeps injections at or below 1 mL for doses up to 10 mg.
Calculate Tirzepatide Dose →The reconstitution steps themselves are identical for both compounds. The math differs because of the different dose ranges. Use the calculator to get exact syringe draws for either.
Results & Research Data
Retatrutide: The Phase 2 trial (published 2023, NEJM) reported mean body weight reduction of approximately 24% at 48 weeks at the 12 mg dose in adults with obesity. Subsequent Phase 3 data from Eli Lilly's TRIUMPH program, with the first readout from TRIUMPH-4 (obesity with knee osteoarthritis, reported December 2025), showed up to 28.7% body weight reduction at 68 weeks on the 12 mg dose. Additional Phase 3 readouts are expected through 2026, with an NDA submission anticipated in late 2026 or early 2027. Retatrutide remains investigational and is not FDA-approved.
Tirzepatide: The SURMOUNT-1 Phase 3 trial reported mean body weight reduction of approximately 22.5% at 72 weeks at the 15 mg dose in adults with obesity without type 2 diabetes. SURMOUNT-2, -3, and -4 replicated substantial reductions across different populations.
These figures are directional summaries of published trial literature. Trial designs, populations, durations, and endpoints differ, so cross-trial comparisons are indicative only — not equivalent to a head-to-head trial. No head-to-head retatrutide vs tirzepatide trial has been published.
Related Guides & Next Steps
Retatrutide Dosage & Reconstitution
Full titration schedule, BAC water tables, syringe draw reference.
Tirzepatide Dosage & Reconstitution
Full titration schedule, BAC water tables, syringe draw reference.
The Retatrutide Protocol Guide →
Complete 9-section research protocol.
The Tirzepatide Protocol Guide →
Complete 10-section research protocol.
Recommended Research Supplier
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Want to see how semaglutide fits in too? View the full 3-way GLP-1 comparison →