Compound Overviews
What Is Retatrutide (GLP-3)? Triple-Agonist Research Overview
Retatrutide — frequently nicknamed "GLP-3" in the research community — is one of the most discussed metabolic research peptides, and the first to act on three incretin receptors at once. This overview is for laboratory and educational reference only.
What is retatrutide?
Retatrutide is a synthetic single-chain peptide (development code LY3437943, from Eli Lilly) described in the literature as a triple-receptor agonist.1 A single molecule activates the GLP-1, GIP, and glucagon receptors. Earlier incretin compounds activated one (semaglutide) or two (tirzepatide) of these receptors — the third axis is what distinguishes it.
The triple agonism
"Incretins" are intestinal hormones that coordinate the body's response to food. Retatrutide combines three axes in one structure:
- GLP-1 — studied for satiety signaling, slowed gastric emptying, and glucose-dependent insulin secretion.
- GIP — studied as a potentiator of insulin response and a modulator of adipose tissue.
- Glucagon (GCGR) — the novel axis, studied for increasing energy expenditure and mobilizing hepatic fat — a different lever than appetite suppression alone.
Mechanism of each receptor
GLP-1: the base
The GLP-1 arm is the best-characterized of the class — appetite signaling in the central nervous system, slower gastric emptying, and glucose-dependent insulin secretion (studied as low-hypoglycemia-risk because it is glucose-dependent).
GIP: the potentiator
GIP's role is more debated, but research suggests that combined with GLP-1 it may improve glycemic and lipid handling in adipose tissue, and may attenuate nausea — a tolerability angle studied in the dual- and triple-agonist literature.
Glucagon: the differentiator
The glucagon arm is the most distinctive. At the liver it is studied for mobilizing fat — a Phase 2a trial in metabolic dysfunction-associated steatotic liver disease (MASLD) reported reductions in liver-fat content in that research population.2 Systemically the glucagon axis is studied for raising energy expenditure. It is also the axis requiring the most attention in research, since the balance among the three receptors in the molecule is deliberately engineered.
Clinical evidence
Phase 2 (obesity) — NEJM 2023
The Phase 2 obesity trial (Jastreboff et al., New England Journal of Medicine, 2023) reported mean weight reductions of up to roughly 24% at 48 weeks in the highest-dose group — among the largest reported for an injectable incretin agonist.3
Phase 2 (type 2 diabetes)
A parallel Phase 2 trial in type 2 diabetes reported significant reductions in HbA1c and body weight, with a safety profile consistent with the class (dose-dependent gastrointestinal effects that improve with titration).4
Phase 3 — the TRIUMPH program
Eli Lilly's Phase 3 program is evaluating retatrutide across obesity (the TRIUMPH trials) and type 2 diabetes (the TRANSCEND trials). The first Phase 3 diabetes readout, TRANSCEND-T2D-1, was published in The Lancet in 2026 and reported significant glycemic and body-weight effects in that trial population, consistent with the earlier Phase 2 signal.5 Phase 3 results across the program are what would inform any eventual regulatory decision — until then, retatrutide remains investigational, and Renova supplies it strictly as a research material.
Retatrutide vs Tirzepatide vs Semaglutide
| Compound | Receptors | Research status |
|---|---|---|
| Semaglutide | GLP-1 (mono) | Approved formulations exist |
| Tirzepatide | GLP-1 + GIP (dual) | Approved formulations exist |
| Retatrutide | GLP-1 + GIP + glucagon (triple) | Phase 3 (investigational) |
The mono → dual → triple progression reflects the strategy of adding hormonal axes to amplify the metabolic effect. For the wider map of the category, see Peptides for Fat Loss: The Complete Research Guide.
Related comparisons: Retatrutide vs Tirzepatide · Retatrutide vs Semaglutide.
Handling and reconstitution
Retatrutide is supplied as a lyophilized (freeze-dried) powder requiring reconstitution with bacteriostatic water before laboratory use; refrigerate (2–8°C) after reconstitution. To work out concentration (mg/mL) for any vial size, see our guides on reconstitution and storage.
Verified purity
Renova Retatrutide is synthesized and lyophilized in the USA and publishes a per-batch third-party COA (HPLC purity, labeled-vs-actual, mass-spec identity, test date). Confirm your lot with Verify Your Vial and read How to Read a Peptide COA.
References
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Kaur M, et al. A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity. Eur J Clin Pharmacol. 2024;80(5):669–676. PMID: 38367045. ↩
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Sanyal AJ, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037–2048. PMID: 38858523. ↩
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Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389:514–526. PMID: 37366315. ↩
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Rosenstock J, et al. Retatrutide for people with type 2 diabetes: a randomised, double-blind, placebo- and active-controlled phase 2 trial. Lancet. 2023;402:529–544. PMID: 37385280. ↩
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Bajaj HS, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes (TRANSCEND-T2D-1): a phase 3 trial. Lancet. 2026;407(10546):2402–2413. PMID: 42250575. ↩
Questions
Frequently Asked
What is retatrutide?
Retatrutide (development code LY3437943) is a synthetic single-chain peptide described in the research literature as a triple-receptor agonist acting on the GLP-1, GIP, and glucagon receptors. It is an investigational compound studied in metabolic and body-weight research.
Why is retatrutide called GLP-3?
"GLP-3" is an informal nickname used in the research community, reflecting that it is seen as a next step beyond GLP-1 (semaglutide) and the GLP-1/GIP dual agonist (tirzepatide). It is not an official receptor name — retatrutide acts on three receptors: GLP-1, GIP, and glucagon.
How is retatrutide different from tirzepatide and semaglutide?
By receptor count. Semaglutide is a mono GLP-1 agonist, tirzepatide is a dual GLP-1/GIP agonist, and retatrutide is a triple GLP-1/GIP/glucagon agonist. The added glucagon axis is the distinguishing feature studied for energy expenditure and hepatic fat mobilization.
Is retatrutide FDA approved?
No. At the time of writing, retatrutide is an investigational compound in Phase 3 trials (the TRIUMPH program) and is not approved by the FDA or any regulatory agency. Renova sells it strictly as a research material, not for human or animal use.
How is retatrutide supplied and stored?
It ships as a lyophilized (freeze-dried) powder, reconstituted with bacteriostatic water for laboratory use and refrigerated (2–8°C) after reconstitution. Use the Reconstitution Calculator to compute concentration for your vial size.
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