What is retatrutide?
Eli Lilly's investigational once-weekly peptide that activates GIP, GLP-1, and glucagon receptors in one molecule (LY3437943).[1]
GIP / GLP-1 / glucagon triple agonist · investigational
Retatrutide (LY3437943)
Investigated for: obesity, type 2 diabetes, MASLD/NASH, sleep apnea
Retatrutide is Eli Lilly's investigational once-weekly injectable peptide that activates three distinct glucose-regulatory receptors — GIP, GLP-1, and glucagon — in a single molecule. It is not FDA-approved. This page summarizes the published Phase 2 trial (NEJM, June 2023) and the December 2025 Phase 3 TRIUMPH-4 readout.
- Sponsor
- Eli Lilly
- Drug code
- LY3437943
- Class
- Triple agonist: GIP + GLP-1 + glucagon[1]
- Dosing route
- Once-weekly subcutaneous (trial design)
- Phase 2 readout
- NEJM 2023 — dose-dependent weight loss at 24/48 wk[1]
- Phase 3 readout (TRIUMPH-4)
- Dec 2025 — ~28.7% avg weight loss at 12 mg over 68 wk[2]
- FDA status
- Not approved (investigational)
- Commercial availability
- None via regulated channels
Investigational drug — educational reference only. Retatrutide is not approved by the FDA and is not commercially available through a pharmacy. Material sold as retatrutide by research-chemical vendors is not the Lilly investigational drug product used in the NEJM and TRIUMPH trials. This page does not recommend dosing, acquisition, or reconstitution guidance for retatrutide.
What retatrutide is
Retatrutide (LY3437943) is a synthetic peptide developed by Eli Lilly as a once-weekly subcutaneous injection for the treatment of obesity and type 2 diabetes. It is distinguished from tirzepatide (also a Lilly compound) by adding activity at the glucagon receptor on top of GIP and GLP-1 agonism — hence "triple agonist."[1] The compound entered Phase 2 obesity trials with results published in the New England Journal of Medicine in June 2023 and has progressed through Phase 3 (TRIUMPH program) with the TRIUMPH-4 weight-management readout reported in December 2025.[1][2]
Mechanism
Retatrutide is a single 39-residue peptide engineered to bind and activate three receptors:
- GIP receptor. Glucose-dependent insulin secretion; additional adipose effects.
- GLP-1 receptor. Glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, central appetite suppression.
- Glucagon receptor. Increased energy expenditure and hepatic glucose output; the glucagon component is hypothesized to contribute to the greater weight-loss efficacy observed in Phase 2 versus GLP-1- or GIP/GLP-1-only agents.[1]
Pharmacokinetic details (half-life, steady-state window, bioavailability) are not yet fully summarized in peer-reviewed literature at the time of this page's review; the FDA prescribing information does not yet exist because the drug is not approved.
Clinical trial status
- Phase 2 obesity trial. Published in NEJM, June 2023 (doi: 10.1056/NEJMoa2301972). Dose-dependent, substantial weight reduction versus placebo at 24 and 48 weeks across 1, 4, 8, and 12 mg weekly doses. Adverse-event profile dominated by dose-dependent GI symptoms consistent with incretin class.[1]
- Phase 3 TRIUMPH program. Multiple registrations on ClinicalTrials.gov (NCT05931367, NCT05929066, NCT05929079, NCT06662383, NCT07035093, NCT07232719) covering obesity, type 2 diabetes, MASLD/NASH, and sleep apnea endpoints.[3]
- TRIUMPH-4 readout (December 2025). Lilly reported participants on the 12 mg weekly dose lost an average 28.7% of body weight (~71 lbs) over 68 weeks.[2]
- Common adverse events at 12 mg in TRIUMPH-4. Nausea 43.2%, diarrhea 33.1%, constipation 25.0%, vomiting 20.9%. Dysesthesia (abnormal skin sensations) reported in up to 21% at the highest doses.[2]
Availability and regulatory status
Retatrutide is not FDA-approved. It is not available from a U.S. pharmacy as of April 2026. Compounding pharmacies are not permitted to compound copies of investigational drugs.
Material sold as "retatrutide" by research-chemical vendors is manufactured and distributed outside the investigational drug supply chain. The identity, purity, and actual content of such material cannot be verified against Lilly's reference standard. This page does not provide reconstitution dosing guidance for retatrutide for two reasons: (1) Phase 3 trial dose levels should not be replicated outside a supervised clinical trial setting, and (2) the research-chemical supply chain does not provide the quality control required to translate such dose levels meaningfully.
Frequently asked questions
Is it FDA-approved?
No. As of April 2026 it is in Phase 3 development. Phase 3 TRIUMPH-4 results were reported in December 2025 but no approval has been granted.[2][3]
How does it work?
Triple agonist — GIP and GLP-1 for glucose regulation, appetite suppression, and delayed gastric emptying; glucagon receptor activation for increased energy expenditure.[1]
What did Phase 3 show?
TRIUMPH-4: average 28.7% weight loss at 12 mg weekly over 68 weeks; GI side effects dominant.[2]
What was the Phase 2 result?
Dose-dependent substantial weight loss at 24 and 48 weeks (NEJM 2023).[1]
Can I buy it?
Not through regulated pharmacy channels. Material sold online as retatrutide is not the Lilly investigational drug product. This page does not recommend acquisition.
Primary references
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple–hormone-receptor agonist retatrutide for obesity — a Phase 2 trial. N Engl J Med, 2023;389:514–526. doi:10.1056/NEJMoa2301972. nejm.org
- Eli Lilly and Company. Retatrutide Phase 3 TRIUMPH-4 results (press disclosure, December 2025). (Full peer-reviewed publication pending.)
- ClinicalTrials.gov — Phase 3 TRIUMPH program entries. NCT05931367, NCT05929066, NCT05929079, NCT06662383.
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