Retatrutide and tirzepatide are two of the most closely followed incretin peptides in current research. Tirzepatide is an established dual GLP-1 / GIP agonist; retatrutide is the next-generation triple agonist (GLP-1 / GIP / glucagon) whose Phase 2 obesity trial (Jastreboff et al., 2023) reported a mean body-weight reduction of up to 24.2% at 48 weeks. This comparison covers mechanism, trial efficacy, reported adverse events, and current regulatory availability.
Mechanism Comparison
| Feature | Retatrutide | Tirzepatide |
|---|---|---|
| Drug class | Triple GLP-1 / GIP / Glucagon receptor agonist | Dual GLP-1 / GIP receptor agonist |
| Code name | LY3437943 | LY3298176 |
| Brand name | None (investigational) | Mounjaro (T2D), Zepbound (obesity, US) |
| Manufacturer | Eli Lilly | Eli Lilly |
| Highest tested cohort | Highest-dose cohort | Highest-dose cohort |
Body-Weight Reduction Efficacy
No direct head-to-head trial has been published. Cross-trial comparison of the retatrutide Phase 2 trial with tirzepatide's SURMOUNT-1 trial (Jastreboff et al., 2022) gives a useful estimate. All four figures are efficacy-estimand results, which count participants while they stayed on treatment, as reported in Lilly's retatrutide and SURMOUNT-1 publication releases:
| Trial | Drug | Mean Body-Weight Reduction | Duration |
|---|---|---|---|
| Phase 2 obesity (NEJM, 2023) | Retatrutide, highest-dose cohort | 24.2% | 48 weeks |
| Phase 2 obesity | Retatrutide, second-highest-dose cohort | 22.8% | 48 weeks |
| SURMOUNT-1 (NEJM, 2022) | Tirzepatide, highest-dose cohort | 22.5% | 72 weeks |
| SURMOUNT-1 | Tirzepatide, mid-dose cohort | 21.4% | 72 weeks |
Retatrutide reached greater body-weight reduction in 48 weeks than tirzepatide achieved in 72, and the body-weight reduction curve had not plateaued at study end, according to the trial's lead investigator, suggesting further reduction with continued treatment duration. Phase 3 results have since been published: in TRIUMPH-1 (Jastreboff et al., 2026), the highest retatrutide dose produced a mean 25.0% body-weight reduction at 80 weeks against 3.9% with placebo, counting all randomised participants (treatment-regimen estimand). On that same basis, the highest tirzepatide dose in SURMOUNT-1 produced 20.9% at 72 weeks. These are cross-trial estimates, so they carry the usual caveats around population differences and trial design.
Diabetes Control (HbA1c)
The Phase 2 type 2 diabetes trial of retatrutide (Rosenstock et al., Lancet, 2023) showed HbA1c reductions of about 2.0 percentage points in the highest-dose cohort at 24 weeks, the primary endpoint, with consistent findings at 36 weeks. That is broadly similar to the 2.01 to 2.30 percentage-point reductions tirzepatide produced over 40 weeks in SURPASS-2 (Frías et al., 2021), its head-to-head trial against semaglutide, although the trials differed in length, comparator and population. A head-to-head trial is required for direct comparison.
Adverse Events Reported in Published Trials
| Adverse Event | Retatrutide, highest-dose cohort (Phase 2) | Tirzepatide, highest-dose cohort (SURMOUNT-1) |
|---|---|---|
| Nausea | 45% | 31% |
| Diarrhoea | 15% | 23% |
| Vomiting | 19% | 12% |
| Heart rate increase | Dose-dependent rise, peaking at 24 weeks then declining | Mean rise of 1 to 3 beats per minute (US label) |
Retatrutide figures are from the trial's results posted on ClinicalTrials.gov (up to 52 weeks including safety follow-up); tirzepatide figures are from Lilly's SURMOUNT-1 publication release, and the heart-rate figure is from the US Zepbound label, so this is a cross-trial comparison. In the retatrutide trial, gastrointestinal events were dose-related, mostly mild to moderate, and partly reduced when treatment started at a lower dose; heart rate rose in a dose-dependent way, peaked at 24 weeks and declined thereafter (Jastreboff et al., 2023).
Availability (October 2026)
| Retatrutide | Tirzepatide | |
|---|---|---|
| MHRA / FDA approval | No. Phase 3 (TRIUMPH) results reported; Lilly plans a US filing in early 2027 | Yes, T2D and obesity |
| NHS access | None | Phased roll-out under NICE TA1026 |
| Research peptide market | Available for laboratory research only | Available for laboratory research only |
Research Peptide Context
Both compounds are widely studied as research peptides for in vitro and pre-clinical work. Retatrutide research material and tirzepatide research material are stocked in factory-direct vials at manufacturer-stated 99%+ purity for laboratory use only. Material sold for research is not for human consumption and must not be used as a substitute for an MHRA-approved prescription.
Comparative Summary
For raw efficacy in obesity trials, current data favours retatrutide, but it remains unapproved. Tirzepatide is the proven, regulator-approved option today. Phase 3 results have started to appear: TRIUMPH-1 and TRIUMPH-2 (Bellido et al., 2026, in people with type 2 diabetes) were published in September 2026, while results from TRIUMPH-3 and TRIUMPH-4 have so far been reported only in Lilly's topline releases (TRIUMPH-4, December 2025; TRIUMPH-3, July 2026).
For the wider GLP-1 research landscape including semaglutide, see the research overview, or the tirzepatide vs semaglutide head-to-head.
References
- Bellido V, et al. (2026). Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. The Lancet. PubMed 42810372
- Coskun T, et al. (2022). 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 Metabolism. PubMed 35985340
- Frías JP, et al. (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine. PubMed 34170647
- Jastreboff AM, et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. PubMed 35658024
- Jastreboff AM, et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. New England Journal of Medicine. PubMed 37366315
- Jastreboff AM, et al. (2026). Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. New England Journal of Medicine. PubMed 42814954
- Rosenstock J, et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. The Lancet. PubMed 37385280
- Sanyal AJ, et al. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. PubMed 38858523