Retatrutide Clinical Research: Phase 1 & Phase 2 Trial Data
Research Programme Overview
Retatrutide (LY3437943) is one of the most extensively published research peptides in the triple-agonist class. Its clinical development followed a structured programme: preclinical receptor characterisation, Phase 1 pharmacokinetic study, Phase 2 randomised trial, and ongoing Phase 3 trials. The published data across these stages represent the scientific foundation that makes retatrutide of high research interest.
The three core published studies are: Coskun et al., Cell Metabolism 2022 (preclinical + receptor characterisation), Urva et al., The Lancet 2022 (Phase 1b), and Jastreboff et al., NEJM 2023 (Phase 2 randomised controlled trial). Each is summarised below.
Preclinical Study: Cell Metabolism 2022
Study design: In vitro receptor binding assays and functional cAMP assays; in vivo studies in diet-induced obese (DIO) mice and non-human primates (NHPs).
Key findings — receptor characterisation: LY3437943 demonstrated binding activity at all three target receptors (GIP, GLP-1, glucagon) with receptor-level potency characterised. Functional assays confirmed receptor activation (agonism) at each target, not merely binding.
Key findings — in vivo DIO mouse model: Compared to a dual GLP-1/GIP agonist reference compound, LY3437943 produced greater changes in body weight and glucose tolerance parameters in diet-induced obese mouse models. Authors attributed this difference in part to the additional glucagon receptor component and its energy-expenditure contributions.
Key findings — NHP pharmacokinetics: Non-human primate pharmacokinetic studies confirmed a half-life compatible with once-weekly dosing — a key criterion for advancing to human trials.
Significance: This study provided the first published characterisation of LY3437943 as a triple GIP/GLP-1/glucagon receptor agonist, establishing the receptor and pharmacokinetic foundation for subsequent clinical investigation.
PMID: 35108511 — Cell Metab. 2022;34(6):882–898.e6
Phase 1 Study: The Lancet 2022
Study design: Multicentre, randomised, double-blind, placebo-controlled Phase 1b study in participants with type 2 diabetes. Participants received escalating doses of LY3437943 over multiple weeks.
Primary objective: Characterise the pharmacokinetics (PK), safety, and tolerability of LY3437943 in humans to support advancement to Phase 2.
Key pharmacokinetic findings: Mean half-life was approximately 7 days, confirming once-weekly dosing was pharmacokinetically supported. Exposure (AUC and Cmax) was dose-proportional across the dose range studied. Time to maximum concentration was consistent across cohorts.
Safety and tolerability: The adverse event profile was broadly consistent with other GLP-1 receptor agonist class compounds. Gastrointestinal adverse events (nausea, vomiting, diarrhoea) were reported, predominantly during the dose-escalation period. No serious unexpected safety signals were identified at the doses studied.
Significance: The Phase 1b data confirmed that the triple-agonist receptor mechanism characterised in preclinical models translated to a pharmacokinetically tractable profile in humans, supporting the Phase 2 programme.
PMID: 36356631 — Lancet. 2022;400(10366):1869–1881
Phase 2 Study: New England Journal of Medicine 2023
Study design: Randomised, double-blind, placebo-controlled Phase 2 dose-ranging study. 338 participants enrolled. Weekly subcutaneous injection over 48 weeks across multiple dose cohorts (1mg, 4mg, 8mg, 12mg escalating doses) vs placebo.
Primary endpoint: Percentage change in body weight at 24 weeks. Secondary endpoint: 48-week data.
Key results (published observations — not therapeutic claims): Substantial reductions in mean body weight were observed across the higher-dose cohorts at both 24 and 48 weeks. The largest reductions were in the 12mg dose group. Dose-response was observed across the cohorts studied.
Safety and tolerability: Gastrointestinal adverse events (nausea, vomiting, diarrhoea) were the most frequently reported adverse events, occurring predominantly during the dose-escalation phase, consistent with the GLP-1 receptor agonist class. The overall safety profile was described by the authors as supporting further investigation in Phase 3.
Significance: This Phase 2 study was among the most discussed in metabolic research in 2023, generating substantial scientific interest in triple-agonist compounds as a mechanistic framework. The published data established retatrutide as a leading compound in the post-tirzepatide generation of incretin receptor research.
PMID: 37366315 — N Engl J Med. 2023;389(6):514–526
Study Summary Table
| Study | Journal & Year | Design | Key finding |
|---|---|---|---|
| Coskun et al. | Cell Metabolism, 2022 | Preclinical (in vitro + DIO mice + NHP) | Triple receptor agonism confirmed; weekly PK profile established in NHPs |
| Urva et al. | The Lancet, 2022 | Phase 1b, RCT, T2D participants | ~7-day half-life confirmed; dose-proportional PK; GLP-1-class tolerability |
| Jastreboff et al. | NEJM, 2023 | Phase 2, 48-week RCT, 338 participants | Substantial body weight changes at higher doses; Phase 3 advancement supported |
Velox Peptides Supply Information
Supplied as a research reagent only. Not a medicine. Not approved by the MHRA or FDA. Not for human or veterinary use. See our Research Use Policy.
References
- Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple GIP, GLP-1 and glucagon receptor agonist for glycemic control and weight loss. Cell Metab. 2022;34(6):882–898.e6. PMID: 35108511
- Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a Phase 1b study. Lancet. 2022;400(10366):1869–1881. PMID: 36356631
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity. N Engl J Med. 2023;389(6):514–526. PMID: 37366315
Frequently Asked Questions
What clinical trials have been conducted on retatrutide?
Three key studies have been published: (1) Coskun et al., Cell Metabolism 2022 — preclinical receptor characterisation and pharmacokinetics; (2) Urva et al., The Lancet 2022 — Phase 1b safety, tolerability and pharmacokinetics in humans; and (3) Jastreboff et al., NEJM 2023 — Phase 2 48-week randomised controlled trial in 338 participants. All summarised here for research reference only.
What did the Phase 2 retatrutide trial find?
The Phase 2 NEJM 2023 trial (Jastreboff et al.) enrolled 338 participants over 48 weeks across multiple dose cohorts. Researchers observed substantial mean body weight reductions in higher-dose groups, with a tolerability profile consistent with GLP-1 class compounds. Published observations — not therapeutic claims.
Is retatrutide approved for human use?
No. As of June 2026, retatrutide is not approved for human use by the MHRA or FDA. It remains in active clinical development (Phase 3). Velox Peptides supplies it strictly for in vitro research use only under our Research Use Policy.
What is the half-life of retatrutide?
The Phase 1 Lancet 2022 study (Urva et al.) confirmed a mean half-life of approximately 7 days in human participants, supporting a once-weekly dosing regimen. This is a published pharmacokinetic observation from clinical research literature.
Where can I buy retatrutide for research in the UK?
Velox Peptides supplies retatrutide (LY3437943) for in vitro research use in the UK. HPLC-verified at ≥99% purity, dispatched from Northern Ireland within 24 hours. View the product page →
