Skip to content
Peptide Insider

GIP, GLP-1 and glucagon receptor triple agonist

Retatrutide

Also known as LY3437943 · Triple hormone receptor agonist · GGG tri-agonist

InvestigationalCLINICALFDA approved: No

Retatrutide adds a third receptor to the incretin story. Alongside GLP-1 and GIP agonism, it activates the glucagon receptor — a counterintuitive choice, since glucagon raises blood glucose, but one grounded in glucagon’s separate effects on energy expenditure and hepatic fat metabolism. The bet was that the metabolic-rate contribution would outweigh the glycaemic one in the context of concurrent incretin agonism. Published Phase 2 results in 2023 suggested it did, and Phase 3 results reported in 2026 put the mean weight reductions above anything previously published for a drug. None of that makes it approved. Retatrutide is an investigational compound, it is widely counterfeited in grey markets on the strength of these headlines, and the distance between "impressive topline result" and "authorised medicine" is exactly the distance this site exists to describe.

Written by Peptide Insider Editorial TeamPublished Last reviewed

The Insider Summary

What it is
An investigational once-weekly peptide that activates three receptors — GIP, GLP-1 and glucagon — developed by Eli Lilly under the code LY3437943.
Why researchers are interested
Adding glucagon receptor agonism targets energy expenditure and hepatic fat in addition to appetite and insulin secretion. Published trials report the largest mean weight reductions of any pharmacological agent to date.
Evidence
Clinical, and still accumulating. A published randomised placebo-controlled Phase 2 trial, followed by Phase 3 results reported in 2026 including the TRIUMPH-1 trial in 2,339 participants.
Regulatory status
Not approved by FDA or any other regulator at the time of writing. It is an investigational drug, available only through clinical trials.
Bottom line
Retatrutide has the strongest efficacy signal in the field and no marketing authorisation. Both facts are load-bearing: the trial results are real and peer-reviewed, and material sold online under this name is not the trial drug, has no quality assurance, and is being taken outside the monitoring that made those results interpretable.

Quick reference

Compound
Synthetic peptide agonist
Research areas
Metabolic Research
Evidence level
CLINICAL
Research status
Investigational
FDA approved
No
Human clinical evidence
Moderate
Last reviewed
17 September 2026

What is retatrutide?

Retatrutide is an investigational once-weekly injectable peptide. "Investigational" has a precise meaning: it is being studied under regulatory oversight in registered clinical trials, it has not been approved for marketing, and it cannot lawfully be sold for the treatment of any condition.

The compound is often described informally as a "GLP-3" or "triple G" agonist. Neither is a formal designation; the accurate description is a GIP, GLP-1 and glucagon receptor triple agonist.

The pharmacological question it tests is specific and interesting: whether adding glucagon receptor agonism — which raises energy expenditure but also, on its own, raises glucose — produces net additional benefit when combined with two incretin agonists that lower glucose.

What do the trials show?

Phase 2 (published 2023). A randomised, double-blind, placebo-controlled trial in adults with obesity reported substantial dose-dependent weight reduction over 48 weeks, materially larger than figures previously published for GLP-1 receptor agonists at comparable time points [1].

Phase 3 TRIUMPH-1 (reported 2026). A randomised, double-blind, placebo-controlled trial enrolling 2,339 participants over 80 weeks, with a pre-specified extension to 104 weeks. The sponsor reported mean weight reductions at 80 weeks of 19.0% (4 mg), 25.9% (9 mg) and 28.3% (12 mg), against 2.2% for placebo. In the extension, participants on 12 mg reached 30.3% at 104 weeks, with 45.3% of participants achieving 30% or greater weight reduction. Discontinuation due to adverse events was reported at 4.1%, 6.9% and 11.3% across the three doses versus 4.9% for placebo [2].

Two caveats belong next to those numbers. First, the Phase 3 figures as cited here come from the sponsor's announcement; the peer-reviewed publication and the regulatory review are the documents that ultimately matter, and this profile will be updated when they are available. Second, the dose-dependent rise in discontinuation for adverse events — from 4.1% to 11.3% — is part of the result, and any honest reading of the efficacy figures has to carry it alongside.

How does Retatrutide work?

Retatrutide is a single peptide with agonist activity at three receptors. GLP-1 receptor agonism enhances glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying and reduces appetite. GIP receptor agonism adds insulinotropic effect and appears to act on adipose tissue and central appetite circuits. Glucagon receptor agonism increases energy expenditure and promotes hepatic lipolysis and fat oxidation — effects that, in the absence of the incretin components, would come with unwanted increases in blood glucose. The design intent is that concurrent incretin agonism offsets that glycaemic effect while the energy-expenditure contribution is retained.

Research and clinical evidence

The table below grades the published record separately for each research area, because a compound can be well studied in one context and entirely unstudied in another. Grades follow the Peptide Insider evidence taxonomy.

Evidence level by research area
Research areaEvidence levelWhat the published record shows
Obesity and weight reductionCLINICALA published randomised placebo-controlled Phase 2 trial plus reported Phase 3 results in 2,339 participants. The largest mean weight reductions published for a pharmacological agent to date.
Type 2 diabetes and glycaemic controlEARLY CLINICALAdditional Phase 3 trials have been reported as successful on weight and HbA1c endpoints. Full publications should be reviewed as they appear.
Long-term safety and cardiovascular outcomesINSUFFICIENTNo long-term outcome data. The compound is too early in development for this question to have been answered.

Human clinical studies

Studies conducted in people. These carry the most weight, and their absence is itself a finding.

Triple–hormone-receptor agonist retatrutide for obesity — a Phase 2 trial[1]

2023
Design
Randomised, double-blind, placebo-controlled, 48 weeks
Population
Adults with obesity

FindingsSubstantial dose-dependent reductions in body weight compared with placebo at 48 weeks, exceeding results previously published for single- and dual-receptor agonists at comparable timepoints. Gastrointestinal adverse events were the most common and were dose-related.

LimitationsPhase 2: designed to establish dose-response and support Phase 3 design, not to demonstrate definitive efficacy or long-term safety. Relatively short duration for a chronic condition.

TRIUMPH-1 — Phase 3 obesity trial (sponsor-reported results)[2]

2026
Design
Randomised, double-blind, placebo-controlled, 80 weeks with pre-specified extension to 104 weeks; once-weekly retatrutide 4 mg, 9 mg, 12 mg or placebo
Population
Adults with obesity
Subjects
2,339 randomised

FindingsReported mean weight reduction at 80 weeks of 19.0%, 25.9% and 28.3% for 4 mg, 9 mg and 12 mg versus 2.2% for placebo. At 104 weeks, the 12 mg group reached 30.3%, with 45.3% of participants achieving at least 30% weight reduction. Common adverse events were nausea, diarrhoea, constipation and vomiting; discontinuation for adverse events was 4.1%, 6.9% and 11.3% versus 4.9% on placebo.

LimitationsThese figures are drawn from the sponsor’s announcement rather than from a peer-reviewed publication or a completed regulatory review. Independent analysis of the full dataset is not yet available. The dose-dependent increase in discontinuations for adverse events is material.

FDA and regulatory status

Retatrutide is not approved by the FDA or by any other regulator we are aware of. It is an investigational drug: lawfully available only to participants in registered clinical trials, under investigator supervision.

That status has a direct practical consequence. Material sold online under the name "retatrutide" is not the investigational product supplied for trials. It has no established identity, purity, sterility or potency, it is not supplied with the monitoring that made the trial results interpretable, and it exists entirely outside the system that produced the evidence people cite when buying it.

If and when retatrutide receives marketing authorisation, this page will be updated with the approved indications and the full label — including the warnings that come with it.

Safety and known risks

Risks are separated into what is documented, what is plausible but unestablished, and what has not been studied. The third column is usually the longest one for an unapproved compound, and it is not a reassurance.

Known risks

Documented in regulatory labelling or published trial safety data.

  • In published and reported trials, the most common adverse events were gastrointestinal: nausea, diarrhoea, constipation and vomiting, dose-related in frequency.
  • In TRIUMPH-1 as reported by the sponsor, discontinuation due to adverse events rose with dose — 4.1%, 6.9% and 11.3% for 4 mg, 9 mg and 12 mg, against 4.9% for placebo.

Potential risks

Plausible on mechanism or drug-class grounds, but not established for this compound.

  • Glucagon receptor agonism raises blood glucose in isolation. The design relies on concurrent incretin agonism to offset this; the balance across different patient populations is still being characterised.
  • Increases in heart rate have been observed across the incretin drug class and warrant attention in longer trials.
  • Class-level regulatory attention to thyroid C-cell findings applies to related approved drugs; retatrutide has no label yet, so no labelled warnings exist to cite.

Unknown or insufficiently studied

Questions the published record does not currently answer.

  • No approved labelling, and therefore no regulator-reviewed statement of contraindications, warnings or interactions.
  • No long-term safety, cardiovascular outcome or mortality data.
  • Effects of weight reduction of this magnitude on lean mass, bone and nutritional status over multi-year periods.

Frequently asked questions

Is retatrutide FDA approved?
No. Retatrutide is an investigational drug. It has not been approved by the FDA or any other regulator, and it is lawfully available only through registered clinical trials.
How much weight did people lose on retatrutide in Phase 3?
In the sponsor-reported TRIUMPH-1 results, mean weight reduction at 80 weeks was 19.0%, 25.9% and 28.3% for the 4 mg, 9 mg and 12 mg doses versus 2.2% on placebo; the 12 mg group reached 30.3% at 104 weeks. These are trial averages from a sponsor announcement, pending peer-reviewed publication.[2]
What makes retatrutide different from semaglutide and tirzepatide?
The number of receptors. Semaglutide targets GLP-1; tirzepatide targets GLP-1 and GIP; retatrutide adds the glucagon receptor, which contributes effects on energy expenditure and hepatic fat metabolism.
Is retatrutide sold online the same as the trial drug?
No. The investigational product is manufactured under pharmaceutical controls and supplied only to trial sites. Material sold online has no verified identity, purity or sterility, and carries none of the monitoring that made the published results meaningful.

Continue reading

Comparison

Semaglutide vs Tirzepatide vs Retatrutide

One, two and three receptors. Two approved drugs and one investigational compound. What the trials measured, what the labels say, and where the differences actually lie.

Regulation

Investigational vs Approved Peptides

Investigational, approved, discontinued and unstudied are four different states, and compounds in all four are sold side by side. How to tell them apart.

Regulation

Are Peptides FDA Approved?

Some peptides are FDA approved drugs. Most compounds sold as "peptides" are not. Here is how to tell the difference, and what approval does and does not mean.

Regulation

How FDA Drug Approval Works

From IND to NDA: the stages a peptide has to pass through to become a medicine, what each one tests, and why most compounds never finish.

References

Peptide Insider cites primary sources wherever they exist — regulatory documents, trial registrations and peer-reviewed literature — in preference to secondary summaries.

  1. 1.
    Jastreboff AM, Kaplan LM, Frías JP, et al.. Triple–hormone-receptor agonist retatrutide for obesity — a Phase 2 trial. The New England Journal of Medicine, 2023.
    Peer-reviewedDOI: 10.1056/NEJMoa2301972PMID: 37366315
  2. 2.
    Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Eli Lilly investor news release, 2026;Published 21 May 2026; TRIUMPH-1.
    InstitutionNCT05929066

    Sponsor announcement. Superseded by peer-reviewed publication and regulatory review when those become available.