Retatrutide vs Tirzepatide: Triple vs Dual Agonist Compared
Two receptors or three? How retatrutide and tirzepatide differ, what the trials show, and what is still unknown.
| Retatrutide receptors | GIP + GLP-1 + glucagon |
|---|---|
| Tirzepatide receptors | GIP + GLP-1 |
| Developer (both) | Eli Lilly and Company |
| Half-life | About 6 days vs about 5 days |
| Status (Nov 2026) | Retatrutide investigational. Tirzepatide approved |
| Head-to-head trial | TRIUMPH-5, expected around end of 2026 |
| Hero products | Hero RT · Hero TZ |
Retatrutide and tirzepatide come from the same lab, use the same design playbook, and share two of their three targets. The difference is one receptor: glucagon. This comparison covers what that extra receptor changes and what the data can and can’t tell us yet.
For the full background on each, see the retatrutide guide and the tirzepatide guide.
Origin story: same family, next generation
Lilly introduced tirzepatide (LY3298176) in 2018 as a dual GIP/GLP-1 agonist (Coskun et al., 2018). Four years later the same team described retatrutide (LY3437943), which adds glucagon receptor activity on a similar backbone (Coskun et al., 2022).
Side by side
| Tirzepatide | Retatrutide | |
|---|---|---|
| Receptors | GIP, GLP-1 | GIP, GLP-1, glucagon |
| Strongest receptor | GIP | GIP |
| Albumin binding | C20 fatty diacid | C20 fatty diacid |
| Half-life | About 5 days | About 6 days |
| Phase 3 program | SURPASS, SURMOUNT | TRIUMPH |
| Status (Nov 2026) | Approved (Mounjaro, Zepbound) | Investigational, filing planned Q1 2027 |
What glucagon adds
Glucagon receptor activation increases energy expenditure and fat oxidation in the liver. GLP-1 and GIP lower glucose, which offsets glucagon’s glucose-raising effect. The result is a compound that targets appetite and energy output. Our receptor explainer covers each receptor in depth.
Trial data compared
| Trial | Compound | Length | Top-dose weight change |
|---|---|---|---|
| SURMOUNT-1 | Tirzepatide | 72 weeks | −20.9% (placebo −3.1%) |
| Phase 2 (Jastreboff 2023) | Retatrutide | 48 weeks | −24.2% (placebo −2.1%) |
| TRIUMPH-1 | Retatrutide | 80 weeks | −28.3% (placebo −2.2%) |
Sources: Jastreboff et al., 2022; Jastreboff et al., 2023; Eli Lilly, May 2026.
Read with care: these are different trials with different populations, lengths and analysis methods. Cross-trial comparisons are rough at best. The direct answer will come from TRIUMPH-5, a head-to-head trial expected to finish around the end of 2026.
Weak spots: safety compared
- Both: gastrointestinal effects (nausea, diarrhea, vomiting) are most common, mostly during dose escalation.
- Retatrutide: heart rate increases were reported in phase 2, peaking and then declining (Jastreboff et al., 2023).
- Long-term data: tirzepatide has years of post-approval data. Retatrutide doesn’t yet.
Handling in the lab
Both ship lyophilized. Hero RT comes in 5 and 10 mg vials, and Hero TZ in 10 and 30 mg. Reconstitute with bacteriostatic water using our reconstitution guide and the calculator.
Retatrutide vs tirzepatide FAQ
Is retatrutide stronger than tirzepatide?
Published retatrutide results are larger, but no head-to-head data exist yet. TRIUMPH-5 will compare them directly.
Do they come from the same company?
Yes. Both were developed by Eli Lilly and Company.
What are Hero RT and Hero TZ?
Hero Peptides’ research-grade retatrutide and tirzepatide, supplied lyophilized for laboratory research use only.
References
- Coskun T, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018;18:3-14.
- Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247.
- Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216.
- Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389(6):514-526.
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Press release, May 21, 2026.
For laboratory research use only. Not for human or veterinary use. This article summarizes published research and is not medical advice.