What Is Retatrutide? The Triple Agonist Peptide Explained

Retatrutide (LY3437943) is an investigational single peptide that activates three receptors: GIP, GLP-1 and glucagon. Online it is sometimes called “GLP-3”, a nickname rather than a scientific name. Adding glucagon receptor activity to dual incretin agonism is the defining idea behind the molecule, and it has now been tested through phase 3.

For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.

Key points

Triple agonist: GIP receptor, GLP-1 receptor and glucagon receptor.
In vitro: balanced glucagon and GLP-1 receptor activity, with greater GIP receptor activity.
Human half-life about 6 days; pharmacokinetics support once-weekly dosing.
Phase 2 (2023) and phase 3 (2026) trials report large dose-related changes in body weight and HbA1c.
“GLP-3” and “GLP-3 RT” are informal labels for retatrutide.

Quick facts

Property	Value
Development code	LY3437943
Class	Lipidated peptide; GIPR/GLP-1R/GCGR triple agonist
Receptor profile (in vitro)	GCGR ≈ GLP-1R; GIPR higher
Half-life (human, phase 1b)	~6 days
Status	Investigational; phase 3 results published 2026

Our retatrutide research peptide is supplied as lyophilized powder in 5–60 mg vials with lot-level HPLC and MS data.

Why add glucagon receptor activity?

Glucagon is usually thought of as a hormone that raises blood glucose. It also increases energy expenditure and affects hepatic lipid metabolism. In Lilly’s discovery paper, retatrutide lowered body weight and improved glycaemic control in obese mice, and the authors attributed part of the weight effect to glucagon-receptor-mediated increases in energy expenditure, added to the reduced calorie intake driven by GIP and GLP-1 receptor agonism (Coskun et al., 2022). Pairing glucagon with incretin agonism is intended to capture the energy-expenditure effect while the incretin components offset glucagon’s glucose-raising action.

Pharmacokinetics

In a 12-week phase 1b multiple-ascending-dose trial in 72 adults with type 2 diabetes, retatrutide showed dose-proportional pharmacokinetics and a half-life of about 6 days. Gastrointestinal events were the most frequently reported adverse events (Urva et al., 2022). In the earlier single-ascending-dose study, effects on body weight persisted up to day 43 after a single administration (Coskun et al., 2022). See retatrutide half-life for details.

Clinical trial endpoints

Trial	Population	Duration	Primary endpoint result (range across dose groups)	Placebo
Phase 2 (Jastreboff et al., 2023)	338 adults with obesity or overweight	48 weeks	Body weight −8.7% to −24.2% at 48 weeks	−2.1%
Phase 3 obesity (Jastreboff et al., 2026)	2339 adults with obesity, no diabetes	80 weeks	Body weight −17.6% to −25.0%	−3.9%
Phase 3 type 2 diabetes, TRANSCEND-T2D-1 (Bajaj et al., 2026)	537 adults, diet and exercise only	Treatment period per protocol	HbA1c −1.69% to −1.94%	−0.81%

The phase 3 obesity trial also included subgroups with knee osteoarthritis (574 participants; WOMAC pain score) and obstructive sleep apnea (243 participants; apnea–hypopnea index), with statistically significant differences versus placebo in both. In all trials the most common adverse events were gastrointestinal and dose-related. These data describe an investigational medicine in controlled clinical trials and do not apply to research material.

Handling research-grade retatrutide

Lyophilized powder; store sealed at −20 °C, protected from light.
Lipidated peptides can self-associate: add solvent slowly, swirl gently and avoid freeze–thaw. See how to reconstitute retatrutide.
Reconstituted solutions: 2–8 °C. See storage guide.
Calculate concentrations with the peptide reconstitution calculator.

Open questions

How much of retatrutide’s effect in humans comes from glucagon receptor agonism versus the incretin components?
How does it compare head-to-head with dual agonists such as tirzepatide?
What are the long-term outcomes beyond the 80-week phase 3 period, including cardiovascular and hepatic endpoints?

Readers following regulatory developments should consult the FDA and EMA directly, since status can change after publication.

Reading the trial numbers: a short glossary

Term	Meaning
Estimand	A precise definition of the treatment effect being estimated, including how events such as stopping treatment are handled
Treatment-regimen (ITT-like) estimand	Includes all randomised participants regardless of adherence; usually gives smaller effects
Least-squares mean	Model-adjusted average used to compare groups
Placebo-adjusted difference	Treatment-group change minus placebo-group change

Two papers on the same molecule can report different numbers simply because they use different estimands, so always check which one a figure refers to.

Related research

Frequently asked questions

What is retatrutide?

Retatrutide (development code LY3437943) is an investigational single peptide with agonist activity at three receptors: the GIP receptor, the GLP-1 receptor and the glucagon receptor.

Why is retatrutide called 'GLP-3'?

‘GLP-3’ is an informal nickname used online because retatrutide acts on three receptors. It is not a scientific name; there is no hormone called GLP-3, and ‘GLP-3 RT’ labels refer to retatrutide.

What is the half-life of retatrutide?

About 6 days in a phase 1b study in people with type 2 diabetes, with dose-proportional pharmacokinetics supporting once-weekly dosing.

How does retatrutide differ from tirzepatide?

Tirzepatide activates GIP and GLP-1 receptors. Retatrutide adds glucagon receptor activity, which in preclinical work increased energy expenditure on top of the reduced calorie intake driven by GIP and GLP-1 receptor agonism.

Is retatrutide approved?

Retatrutide is investigational. Phase 3 results in obesity and type 2 diabetes were published in 2026; regulatory status should be checked with the FDA or EMA for the latest position.

References

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. PMID: 35985340 https://pubmed.ncbi.nlm.nih.gov/35985340/
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. PMID: 36354040 https://pubmed.ncbi.nlm.nih.gov/36354040/
Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial. N Engl J Med. 2023. PMID: 37366315 https://pubmed.ncbi.nlm.nih.gov/37366315/
Jastreboff AM, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. 2026. PMID: 42814954 https://pubmed.ncbi.nlm.nih.gov/42814954/
Bajaj HS, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet. 2026. PMID: 42250575 https://pubmed.ncbi.nlm.nih.gov/42250575/