Retatrutide (LY3437943): Triple-Receptor Agonist Profile and the Published Phase 2 and Phase 3 Record

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Retatrutide is one of the most-discussed peptides in metabolic research, and in 2026 it became one of the few research-market compounds with a published Phase 3 record. This guide summarizes what the peer-reviewed literature contains, how to read its numbers, and how the material is handled in a research setting. It is written for researchers and is not medical guidance.

Research-use note: Retatrutide is an investigational compound supplied strictly for laboratory research. It is not an approved drug, not a supplement, and not for human or animal consumption. Nothing below describes, recommends or implies use in people.

Evidence at a glance

Phase 3 trials, not yet approved

Retatrutide now has published Phase 3 results in obesity and type 2 diabetes (2026), following the Phase 2 trials of 2023. It is still investigational and is not approved.

Why researchers are interested

It works on three receptors, GIP, GLP-1 and glucagon, where earlier drugs work on one or two. The glucagon arm is the addition that matters, because it raises energy expenditure on top of the appetite reduction the others provide. That is the accepted explanation for why its trial results beat them.

What the research found

• Large weight reduction in Phase 3Mean body weight change of -25.0 percent at 12 mg over 80 weeks against -3.9 percent with placebo, counting everyone randomised (TRIUMPH-1, NEJM 2026)
• Weight and blood sugar in type 2 diabetesMean body weight change of -18.8 percent at 12 mg over 80 weeks (TRIUMPH-2, Lancet 2026); HbA1c reductions of up to 1.94 points at 40 weeks (TRANSCEND-T2D-1, Lancet 2026)
• Less liver fatRelative liver fat reduction of up to 82 percent at 24 weeks in a Phase 2a substudy (Sanyal, Nature Medicine 2024)
• Triple receptor activity confirmedReceptor pharmacology characterised (Coskun, 2022); half-life of about six days in Phase 1b (Urva, Lancet 2022)

Reported in the literature

• Gastrointestinal effects were the most common in every trial, including nausea, vomiting, diarrhoea and constipation, and they rose with dose.
• Increases in heart rate were observed in Phase 2.
• In TRIUMPH-2, dysesthesia (an abnormal skin sensation) and low blood pressure were more frequent than with placebo, and 8 to 12 percent stopped treatment for adverse events against 5 percent.
• Long term safety is unknown. The cardiovascular and kidney outcomes trial is not expected to complete before 2029.

Findings are summarised from the sources listed under References on this page, and from approved product labelling where a compound has one. These are outcomes observed in published studies, not effects claimed for any person, and nothing here is a recommendation for human use.

What is retatrutide?

Retatrutide is a synthetic peptide developed by Eli Lilly under the code LY3437943 and engineered so that one molecule activates three receptors: the GIP receptor, the GLP-1 receptor and the glucagon receptor. That three-way design is the reason it occupies the place it does in metabolic research.

It is an investigational compound. It has been examined in company-run clinical trials through Phase 3 and is not approved by any regulatory authority for medical use. In the research-peptide market it is often called GLP-3 or reta. GLP-3 is a market nickname rather than a receptor class or an official designation; there is no third GLP receptor that the name would refer to.

Where it sits among incretin compounds

The clearest way to place these compounds is by counting the receptors each one engages, because that is the structural difference the literature is organised around.

• Single agonist: GLP-1 receptor only. The earliest and largest body of incretin work.
• Dual agonist: GIP and GLP-1 receptors. Tirzepatide is the reference compound for this class.
• Triple agonist: GIP, GLP-1 and glucagon receptors. Retatrutide.

The glucagon-receptor component is the defining addition. Glucagon signalling is conventionally discussed in opposition to insulin signalling, so a molecule deliberately engaging that receptor alongside two incretin receptors is a departure from how the earlier compounds were designed, and that is why the preclinical pharmacology drew attention.

How retatrutide works (the mechanism studied)

The preclinical molecular pharmacology was characterised by Coskun and colleagues in Cell Metabolism (2022), which described how the single peptide engages all three receptors and reported the relative potency at each.

The first human pharmacology came from a Phase 1b study by Urva and colleagues (The Lancet, 2022) in 72 dosed participants with type 2 diabetes. It reported dose-proportional pharmacokinetics and a half-life of approximately six days, which is the basis for the once-weekly schedule used in every later trial.

For laboratory purposes the practical consequence of the triple design is that retatrutide cannot be treated as a drop-in comparator for a single- or dual-agonist compound. Any experiment comparing it to tirzepatide is comparing two different receptor profiles, not two doses of the same thing.

What the published trial record contains

The retatrutide literature is unusual for a research-market peptide in that almost all of it is clinical-trial data generated or funded by the developer rather than scattered academic work. The peer-reviewed record, in order of publication, is below. Figures are the papers' own primary results for the populations and protocols studied.

• Phase 2, obesity (Jastreboff et al., New England Journal of Medicine, 2023). 338 adults. At 48 weeks the mean change in body weight ranged from -8.7% at 1 mg to -24.2% at 12 mg, against -2.1% with placebo.
• Phase 2, type 2 diabetes (Rosenstock et al., The Lancet, 2023). 281 participants. At 24 weeks HbA1c changed by up to -2.02% in the 12 mg escalation group, against -0.01% with placebo and -1.41% with the active comparator dulaglutide 1.5 mg.
• Phase 2a, liver fat (Sanyal et al., Nature Medicine, 2024). A substudy of 98 participants from the obesity trial who had metabolic dysfunction-associated steatotic liver disease and at least 10% liver fat. The relative change in liver fat at 24 weeks ranged from -42.9% at 1 mg to -82.4% at 12 mg, against +0.3% with placebo.
• Phase 2, body composition (Coskun et al., Lancet Diabetes and Endocrinology, 2025). A DXA substudy of the diabetes trial. Total fat mass fell by 15.2% (4 mg), 26.1% (8 mg) and 23.2% (12 mg) at 36 weeks, against 4.5% with placebo, in the 103 participants who completed both scans.
• Phase 3, type 2 diabetes (TRANSCEND-T2D-1; Bajaj et al., The Lancet, 2026). 537 participants managed with diet and exercise alone. At 40 weeks HbA1c changed by -1.69% to -1.94% across the 4, 9 and 12 mg doses, against -0.81% with placebo.
• Phase 3, obesity (TRIUMPH-1; Jastreboff et al., New England Journal of Medicine, 2026). 2,339 adults with obesity and without diabetes, treated for 80 weeks. Mean body-weight change was -17.6%, -23.7% and -25.0% at 4, 9 and 12 mg, against -3.9% with placebo. The trial also measured knee-osteoarthritis pain scores in a subgroup of 574 and the apnea-hypopnea index in a subgroup of 243 with obstructive sleep apnea.
• Phase 3, obesity with type 2 diabetes (TRIUMPH-2; Bellido et al., The Lancet, 2026). 1,152 participants treated for 80 weeks. Mean body-weight change was -11.9%, -16.8% and -18.8% at 4, 9 and 12 mg, against -5.1% with placebo.

Further Phase 3 programmes are listed on ClinicalTrials.gov, including a head-to-head comparison with tirzepatide in adults with obesity (NCT06662383) and a cardiovascular and kidney outcomes trial, TRIUMPH-Outcomes (NCT06383390), whose primary completion is estimated for February 2029.

Adverse findings reported in the trials

Gastrointestinal events were the most common adverse events in every trial listed above, and they rose with dose. In the Phase 2 obesity trial they were mostly mild to moderate and were partly reduced by a lower starting dose.

The Phase 2 obesity trial also reported dose-dependent increases in heart rate that peaked at 24 weeks and declined afterwards.

TRIUMPH-2 reported two findings more often with retatrutide than with placebo that are less familiar from earlier incretin compounds: dysesthesia, an abnormal skin sensation, in 4% to 7% of participants against 1%, and hypotension in 1% to 6% against under 1%. Permanent discontinuation because of adverse events was 12% at 9 mg and 8% at 12 mg, against 5% with placebo.

Long-term outcome data does not yet exist. The cardiovascular and kidney outcomes trial is still running.

Reading the numbers correctly

Retatrutide figures quoted online often disagree, and most of the disagreement has three sources.

Estimands. Phase 3 papers report results two ways. A treatment-regimen estimand counts everyone randomised, including people who stopped the drug. An efficacy estimand counts only people who stayed on treatment, so its figures are larger. TRIUMPH-1's 12 mg result is -25.0% under the treatment-regimen estimand; the 28.3% figure that circulated after Lilly's May 2026 announcement was the on-treatment figure. Both are correct and they answer different questions.

Populations. Results in people with type 2 diabetes are consistently smaller than in people without it; TRIUMPH-2's -18.8% at 12 mg and TRIUMPH-1's -25.0% are not in conflict. Trial durations also differ: 24, 36, 40, 48 and 80 weeks appear in the papers above.

Source type. Press releases and topline announcements come before peer review and sometimes report extension or subgroup figures. For anything that matters, read the primary paper rather than a summary, including this one.

Regulatory status

As of October 2026 retatrutide is not approved by the FDA or any other regulator. Lilly has stated that it plans to submit a Biologics License Application to the FDA in the first quarter of 2027, as reported in July 2026. Until a regulator approves it, every published result above describes an investigational drug candidate in a defined trial population, not an approved or validated use.

Handling and reconstitution in the laboratory

Retatrutide is supplied as a lyophilized powder for research use. Standard laboratory practice is to reconstitute with bacteriostatic water, swirl rather than shake until fully dissolved, and store the reconstituted solution refrigerated at 2-8 degrees Celsius. The sealed lyophilized vial is kept frozen and protected from light.

As with any lyophilized peptide, repeated freeze-thaw cycles are avoided, and the material is allowed to reach room temperature before the vial is opened to limit condensation.

These are general handling notes for laboratory material rather than instructions for use, and they do not replace the protocol in force in the receiving laboratory. See how to reconstitute peptides for the full process.

For research use only

All products and information referenced here are intended strictly for laboratory and scientific research use. They are not for human or animal consumption and are not drugs, foods, supplements, or medical devices. Retatrutide is an investigational compound that has not been approved by any regulatory authority for medical use.

Nothing on this page is medical advice. Products are supplied against a stated purity specification, and buyers are expected to be qualified researchers or institutions.

Explore retatrutide and related research peptides

• Retatrutide (GLP-3), 10mg and 20mg research vials
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• Bacteriostatic Water 30ml, reconstitution diluent
• Full research catalog

Common questions about Retatrutide

Is "reta" or "GLP-3" the same as retatrutide?

Yes. Both are informal nicknames for retatrutide, developmental code LY3437943 (CAS 2381089-83-2). "GLP-3" refers to its three receptor targets rather than an official drug class.

Is retatrutide approved?

No. Retatrutide is an investigational compound and is not approved by any medicines regulator. Phase 2 results were published in 2023 and Phase 3 results in 2026, and Lilly has said it plans to file with the FDA in early 2027.

How is retatrutide different from tirzepatide?

Tirzepatide activates the GIP and GLP-1 receptors; retatrutide adds the glucagon receptor. See the tirzepatide vs retatrutide comparison.

How is retatrutide stored?

As a lyophilized powder, frozen and protected from light. Once reconstituted with bacteriostatic water it is kept refrigerated at 2 to 8 °C. See the reconstitution guide.

References

1. 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. PubMed
2. Urva S, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022. PubMed
3. Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial. N Engl J Med. 2023. PubMed
4. Rosenstock J, et al. 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. Lancet. 2023. PubMed
5. Sanyal AJ, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024. PubMed
6. Coskun T, et al. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2 randomised trial. Lancet Diabetes Endocrinol. 2025. PubMed
7. Bajaj HS, et al. Efficacy and safety of retatrutide in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a phase 3 trial. Lancet. 2026. PubMed
8. Jastreboff AM, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). N Engl J Med. 2026. PubMed
9. Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a phase 3 trial. Lancet. 2026. PubMed
10. ClinicalTrials.gov. NCT06662383 (retatrutide vs tirzepatide) and NCT06383390 (TRIUMPH-Outcomes). Accessed October 9, 2026.
11. Drugs.com. Retatrutide FDA approval status. Updated July 2026. drugs.com

Related comparison: Tirzepatide vs Retatrutide, how the research compounds compare.