Compound monograph
Retatrutide
Also known as: LY3437943
§1 Definition
Retatrutide is an investigational injectable peptide that activates the GIP, GLP-1, and glucagon receptors simultaneously (a "triple agonist"), developed by Eli Lilly for obesity and type 2 diabetes. As of September 2026 it remains in Phase 3 trials (the TRIUMPH program) and is not FDA-approved; in trials, the highest studied dose has produced average weight loss exceeding 28% over 80 weeks.
Educational purposes only, not medical advice. Dosing figures below are documented ranges from cited literature, not a recommendation for any individual. Consult a qualified provider before administering anything.
§2 Evidence tier and regulatory status
Evidence tier
2 — Late-phase trials
Not yet FDA-approved, but in Phase 2 or Phase 3 clinical trials with published human data.
Investigational; not FDA-approved. In Phase 3 clinical trials (the TRIUMPH program) as of September 2026. The sponsor (Eli Lilly) has publicly indicated an NDA submission is anticipated in 2026, though no FDA decision date has been confirmed. A pre-approval expanded access protocol (ClinicalTrials.gov NCT07629401) opened in June 2026.
§3 Documented dosing
| Context | Range | Frequency | Source |
|---|---|---|---|
| Phase 2 obesity trial (not FDA-approved dosing — trial arms studied) | 1–12 mg | once weekly, 48 weeks | [1] |
| TRIUMPH-1, Phase 3 (obesity/overweight without diabetes) — trial arms studied | 4–12 mg | once weekly, 80 weeks | [3], [5] |
| TRIUMPH-2, Phase 3 (obesity + type 2 diabetes) — trial arms studied | 4–12 mg | once weekly, 80 weeks | [4] |
| TRIUMPH-3, Phase 3 (obesity + established cardiovascular disease) — trial arms studied | 9–12 mg | once weekly, 80 weeks | [4] |
These are trial dose arms, not an approved or recommended dosing schedule — retatrutide has no FDA-approved indication or label as of this writing.
§4 Reconstitution math
Trial drug product is delivered via a prefilled pen or syringe, not reconstituted from lyophilized powder — no published reconstitution protocol exists for the trial formulation. Retatrutide sold on the research-chemical market is typically supplied as a lyophilized vial; the sizes listed above reflect what such sellers commonly offer, not a documented clinical or manufacturer specification, since retatrutide has no FDA-approved commercial product yet.
| Vial | Water | Concentration | Draw volume | Units (U-100) |
|---|---|---|---|---|
| 5 mg | 2.0 mL | 2500 mcg/mL | 0.4 mL | 40.0 |
| 10 mg | 2.0 mL | 5000 mcg/mL | 0.2 mL | 20.0 |
| 15 mg | 2.0 mL | 7500 mcg/mL | 0.133 mL | 13.3 |
- Concentration
- 2500 mcg/mL
- Draw volume
- 0.4 mL
- Syringe units
- 40.0
- Doses per vial
- 5
§5 What the research shows
| Trial | Phase | n | Duration | Endpoint | Result | Source |
|---|---|---|---|---|---|---|
| Phase 1b multiple-ascending-dose trial | Phase 1b | 72 | 12 weeks | Safety, tolerability, and pharmacokinetics in adults with type 2 diabetes | Dose-proportional pharmacokinetics supporting once-weekly dosing; safety profile broadly consistent with other incretin-based therapies. | [2] |
| Phase 2 obesity trial (Jastreboff et al.) | Phase 2 | 338 | 48 weeks | Percent body weight change in adults with obesity (without diabetes) | Least-squares mean weight change at 48 weeks: -8.7% (1mg), -17.1% (4mg), -22.8% (8mg), -24.2% (12mg) vs -2.1% with placebo. | [1] |
| TRIUMPH-1 | Phase 3 (sponsor topline results, not yet peer-reviewed) | 2339 | 80 weeks | Percent body weight change in adults with obesity/overweight without diabetes | 12mg arm: -28.3% mean weight change (-70.3 lbs); 45.3% of participants achieved ≥30% weight loss. Sponsor-reported topline results, not yet published in a peer-reviewed journal. | [3], [5] |
| TRIUMPH-2 | Phase 3 (sponsor topline results, not yet peer-reviewed) | 1152 | 80 weeks | Percent body weight change and A1C reduction in adults with obesity and type 2 diabetes | Weight loss of 12.7% / 19.1% / 20.8% (4mg / 9mg / 12mg) vs 4.0% with placebo; A1C reduction up to 1.6 percentage points. Sponsor-reported topline results, not yet peer-reviewed. | [4] |
| TRIUMPH-3 | Phase 3 (sponsor topline results, not yet peer-reviewed) | 1949 | 80 weeks | Percent body weight change in adults with obesity and established cardiovascular disease | Weight loss of 21.6% / 22.6% (9mg / 12mg) vs 3.2% with placebo. Sponsor-reported topline results, not yet peer-reviewed. | [4] |
§6 Safety and reported adverse effects
| Effect | Incidence | Source |
|---|---|---|
| Nausea (Phase 2, 12mg arm) | 60% | [1] |
| Nausea (TRIUMPH-2, 12mg vs placebo) | 28.0% vs 8.0% | [4] |
| Diarrhea (TRIUMPH-2, 12mg vs placebo) | 33.6% vs 13.2% | [4] |
| Constipation (TRIUMPH-2, 12mg vs placebo) | 16.8% vs 9.4% | [4] |
| Decreased appetite (TRIUMPH-2, 12mg vs placebo) | 17.1% vs 4.5% | [4] |
| Discontinuation due to adverse events (TRIUMPH-2 vs placebo) | 7.7% vs 4.9% | [4] |
TRIUMPH-1/2/3 adverse-event rates come from sponsor topline press releases, not yet published in a peer-reviewed paper — treat these as preliminary until formal publication.
Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) — a trial exclusion criterion, consistent with the wider GIP/GLP-1/glucagon receptor agonist class
- History of pancreatitis — a trial exclusion criterion
Known interactions
- No published drug-interaction data located beyond the trial exclusion criteria listed above.
§7 Storage and handling
- Lyophilized
- No published data located.
- Reconstituted
- No published data located.
§8 Sourcing considerations
- Since retatrutide is investigational and not FDA-approved, any product sold as "retatrutide" outside a clinical trial is unregulated and research-use-only by definition.
- Verify lab-reported purity and identity testing from an independent third party, since there is no FDA-approved reference product to compare against.
- Be aware that the trial drug product is pen/syringe-delivered, not a lyophilized vial — research-market vials come from a separate, unregulated supply chain.
§9 FAQ
Is retatrutide FDA approved?
No. As of September 2026 it remains investigational, in Phase 3 trials (the TRIUMPH program). The sponsor has indicated an NDA submission is anticipated later in 2026, but no FDA decision date has been confirmed.
What phase of trials is retatrutide in?
Phase 3 — the TRIUMPH-1, TRIUMPH-2, and TRIUMPH-3 trials, which had all reported sponsor topline results by mid-2026 but were not yet published in a peer-reviewed journal as of this writing.
How much weight can you lose on retatrutide?
In TRIUMPH-1 (sponsor topline results, not yet peer-reviewed), the 12mg arm averaged -28.3% body weight change over 80 weeks. In the earlier peer-reviewed Phase 2 trial, the 12mg arm averaged -24.2% over 48 weeks.
What are retatrutide's side effects?
Gastrointestinal effects — nausea, diarrhea, constipation, and decreased appetite — increase with dose across the trials. See the adverse effects table above for reported incidence rates.
Is retatrutide the same as tirzepatide?
No. Tirzepatide is a dual GIP/GLP-1 receptor agonist. Retatrutide additionally activates the glucagon receptor, making it a triple agonist.
When will retatrutide be approved?
Not yet. The sponsor has publicly indicated an NDA submission is anticipated in 2026, but there is no confirmed FDA approval date.
What is the half-life of retatrutide?
Approximately 6 days, which supports once-weekly dosing — see the half-life note above on this figure's confidence level.
Is retatrutide safe?
Its trial safety profile so far is broadly similar to other incretin-class drugs, mainly dose-dependent gastrointestinal effects, but as an investigational compound its long-term safety has not been established the way an FDA-approved drug's has.
§10 Sources
- [1] Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine, 2023. Peer-reviewed. https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
- [2] LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multiple-ascending-dose trial. The Lancet, 2022. Peer-reviewed. https://www.sciencedirect.com/science/article/abs/pii/S0140673622020335
- [3] Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1 topline results). Eli Lilly and Company, 2026. Other. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss
- [4] Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3 topline results). Eli Lilly and Company, 2026. Other. https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html
- [5] A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Overweight (TRIUMPH-1). ClinicalTrials.gov, 2023. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05929066
- [6] Pre-approval Expanded Access of Retatrutide (LY3437943). ClinicalTrials.gov, 2026. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT07629401