What is retatrutide and how does it work?

It is a single synthetic peptide that acts as a triple agonist at the GLP-1, GIP, and glucagon receptors. Researchers reported it binds human GCGR, GIPR, and GLP-1R with EC50 values of roughly 5.79, 0.0643, and 0.775 nM, with combined receptor activity hypothesized to affect appetite, insulin secretion, energy expenditure, and hepatic lipid handling.

What did the phase 2 studies report?

In a 48-week phase 2 obesity trial (n=338), investigators observed a least-squares mean body-weight change of −24.2% in the 12 mg group versus −2.1% with placebo. A phase 2 type 2 diabetes trial reported HbA1c reductions of about 2 percentage points in higher-dose groups, and a phase 2a MASLD trial reported liver-fat normalization in up to 86% of participants. These are research findings, not clinical guidance.

What is the molecular formula and weight of retatrutide?

Per PubChem (CID 171934787), the molecular formula is C221H342N46O68 with a molecular weight of approximately 4731 g/mol and InChIKey MLOLQJNKXBNWFW-JMUPIODPSA-N. The CAS registry number reported by suppliers is 2381089-83-2.

Retatrutide Dosage, Half-Life & Research

Q: Is retatrutide an approved drug, or is it research-use-only?

Retatrutide (LY3437943) is an investigational compound supplied strictly for research use only. It is not an approved drug in Canada or elsewhere and is not authorized for human or veterinary use, diagnosis, or treatment. As of this writing, published human data are limited to phase 1 and phase 2 trials.

Retatrutide (developmental code LY3437943) is an investigational, once-weekly synthetic peptide that acts as a single-molecule agonist at three receptors at once: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GCGR).¹ It is offered here strictly for research use only. Retatrutide is not an approved drug in Canada or elsewhere and is not authorized for human or veterinary use, diagnosis, or therapy. It remains under clinical investigation; as of this writing the published human evidence is limited to phase 1 and phase 2 trials.² The data summarized below describe what researchers observed in those studies and should not be read as guidance for use in people.

Structure

Sequence & identity

39-amino-acid modified peptide (not a simple linear sequence) · C₂₂₁H₃₄₂N₄₆O₆₈ · 4731 g/mol

Chemical identity confirmed against PubChem (CID 171934787; InChIKey MLOLQJNKXBNWFW-JMUPIODPSA-N).⁵ Structure is not a simple linear peptide: it incorporates non-coded residues (Aib at positions 2 and 20, α-methyl-leucine at 13) and a C20 fatty-diacid moiety conjugated via a linker at Lys17 to enable albumin binding.¹

What the research shows

Mechanisms studied

Researchers reported that retatrutide is a single peptide derived from a GIP backbone that engages three incretin/metabolic receptors simultaneously.¹ In the discovery and characterization work by Coskun and colleagues, the molecule bound human GCGR, GIPR, and GLP-1R with EC₅₀ values of approximately 5.79, 0.0643, and 0.775 nM respectively, indicating relatively greater potency at GIPR.¹ The investigators proposed that combined GLP-1R and GIPR activation drives appetite reduction and improved insulin secretion, while added GCGR agonism may raise energy expenditure and influence hepatic lipid handling — a combination they hypothesized could exceed dual agonists in metabolic models.¹ The conjugated C20 fatty diacid promotes albumin binding, which researchers reported extends the plasma half-life to roughly 6 days and supports once-weekly dosing in trials.¹²

Reported in studies

Dosing in the research literature

The figures below summarise regimens as reported in published research — they are not recommendations or directions for use.

Source / model	Regimen reported	Notes
Jastreboff AM et al., N Engl J Med 2023 (phase 2 obesity)²	Once-weekly subcutaneous administration was studied across groups reaching maintenance levels of 1, 4, 8, and 12 mg, using gradual dose-escalation schedules over 48 weeks (n=338).	Reported in a human study only; listed to document the regimen investigators used, NOT as directions for use. Retatrutide is research-use-only and not an approved drug.
Rosenstock J et al., Lancet 2023 (phase 2, type 2 diabetes)³	Once-weekly subcutaneous administration with maintenance groups of 0.5, 4, 8, and 12 mg (plus dulaglutide and placebo comparators), with escalation over 36 weeks (n=281).	Study-reported regimen for documentation only. No usage directions are implied.
Sanyal AJ et al., Nat Med 2024 (phase 2a, MASLD)⁴	Once-weekly subcutaneous administration at maintenance doses of 1, 4, 8, and 12 mg over 48 weeks (n=98).	As reported in the cited trial. Not a recommendation; retatrutide is investigational.

Research use only. Peptigo products are sold to qualified researchers for laboratory use. This information summarises published research for reference and is not medical advice, a dosing recommendation, or directions for human or animal use.

Reported in studies

Effects observed in research

In a 48-week phase 2 obesity trial, investigators observed a least-squares mean change in body weight of −8.7% (1 mg), −17.1% (4 mg), −22.8% (8 mg), and −24.2% (12 mg), versus −2.1% in the placebo group.² In a phase 2 trial in adults with type 2 diabetes, researchers reported HbA1c reductions of roughly 2.0–2.2 percentage points in the higher-dose groups alongside substantial weight reduction.³ In a phase 2a study in metabolic dysfunction–associated steatotic liver disease (MASLD), the authors observed normalization of liver fat (below 5%) in 27%, 52%, 79%, and 86% of participants in the 1, 4, 8, and 12 mg groups at 24 weeks, versus 0% with placebo.⁴ Across these trials the most frequently reported adverse events were gastrointestinal — nausea, vomiting, and diarrhea — generally dose-related and consistent with the incretin-agonist class.²³ These are research findings in clinical-trial populations and are described here for scientific context only.

Honest assessment

Strength of evidence

Grade B

Grade B. The human evidence base consists of randomized, placebo-controlled phase 1 and phase 2 trials with consistent, dose-dependent metabolic effects, supported by mechanistic and preclinical characterization.¹²³⁴ However, no phase 3 outcome trials have been published at the time of writing, long-term safety and cardiovascular/renal outcomes are not yet established, and retatrutide is not an approved medicine. Reported dosing reflects trial protocols, not validated clinical regimens. Findings should be regarded as promising but preliminary, and all values above were verified against primary literature and PubChem; where a parameter could not be confirmed it is marked as not established.

Handling

Reconstitution & storage

Reconstitute with bacteriostatic water for laboratory handling. Store lyophilised material frozen and reconstituted material refrigerated. Use Peptigo’s reconstitution calculator and storage cheat sheet for working figures.

References

Coskun T, Urva S, Roell WC, 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;34(9):1234-1247.e9. DOI: 10.1016/j.cmet.2022.07.013
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(6):514-526. DOI: 10.1056/NEJMoa2301972
Rosenstock J, Frias J, Jastreboff AM, 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 conducted in the USA. Lancet. 2023;402(10401):529-544. DOI: 10.1016/S0140-6736(23)01053-X
Sanyal AJ, Bedossa P, Fraessdorf M, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024. DOI: 10.1038/s41591-024-03018-2
National Center for Biotechnology Information. PubChem Compound Summary for CID 171934787, Retatrutide (sodium salt). InChIKey MLOLQJNKXBNWFW-JMUPIODPSA-N; Molecular Formula C221H342N46O68. https://pubchem.ncbi.nlm.nih.gov/compound/171934787

Written by the Peptigo Research Team · scientifically reviewed by Peter, Peptigo Research Team · Last reviewed June 2026. We cite primary literature and flag where evidence is limited. Our sourcing & RUO policy →