Retatrutide (LY3437943) is an investigational peptide from Eli Lilly that activates three hormone receptors with one molecule: GIP, GLP-1 and glucagon. In a 48-week phase 2 trial, people with obesity on the highest dose lost on average 24.2% of their body weight. It is now in phase 3 trials and is not an approved medicine.[3]
Retatrutide at a glance
- Type: triple agonist of the GIP, GLP-1 and glucagon receptors, 39 amino acids, about 4731 g/mol.
- Developer: Eli Lilly; first described in 2022.[1]
- Half-life: about 6 days – given once weekly in trials.[2]
- Best-known result: −24.2% mean body weight after 48 weeks at 12 mg.[3]
- Status: phase 3 (TRIUMPH, TRANSCEND), not approved by the EMA or FDA.
How does Retatrutide work?
After a meal the gut releases two incretin hormones, GLP-1 and GIP. Both increase insulin secretion when blood sugar is high, and GLP-1 also slows stomach emptying and signals fullness to the brain. The third hormone, glucagon, is produced by the pancreas; besides raising blood sugar it increases energy expenditure and the breakdown of fat in the liver.
Retatrutide was engineered to activate all three receptors in one balanced molecule. In laboratory tests it is more potent than natural GIP at the GIP receptor and weaker than the native hormones at the GLP-1 and glucagon receptors – a balance chosen so that the incretin effect counteracts the blood-sugar rise from glucagon.[1]
What is the structure of Retatrutide?
The backbone is a 39-amino-acid chain based on the GIP sequence, with three non-standard amino acids (two Aib and one α-methyl-leucine) that protect it from breakdown by the enzyme DPP-4. A C20 fatty diacid is attached to a lysine side chain through a short linker. This fatty acid binds albumin in the blood, which slows clearance by the kidneys and extends the half-life to about six days.[1][2] The molecular formula is C221H342N46O68 and the CAS number 2381089-83-2.
What did the clinical trials show?
The first human study (phase 1b, 12 weeks) in people with type 2 diabetes confirmed the long half-life and showed dose-dependent falls in blood glucose and body weight.[2] It was followed by two phase 2 trials published in 2023.
In the obesity trial, 338 adults with obesity or overweight received placebo or a weekly dose of 1, 4, 8 or 12 mg for 48 weeks. Mean weight change was −2.1% with placebo, −8.7% at 1 mg, −17.1% at 4 mg, −22.8% at 8 mg and −24.2% at 12 mg. Weight was still falling at the end of the trial in the highest dose groups.[3]
In the type 2 diabetes trial (281 participants, 36 weeks), HbA1c fell by up to about 2 percentage points and body weight by up to about 17% in the higher dose groups, with Dulaglutide used as an active comparator.[4]
| Weekly dose | Weight change after 48 weeks |
|---|---|
| Placebo | −2.1% |
| 1 mg | −8.7% |
| 4 mg | −17.1% |
| 8 mg | −22.8% |
| 12 mg | −24.2% |
Does Retatrutide reduce liver fat?
A substudy of the obesity trial measured liver fat by MRI in participants with metabolic dysfunction-associated steatotic liver disease (MASLD). At the 8 and 12 mg doses liver fat fell by more than 80% relative to baseline, and in most participants it dropped below the 5% threshold considered normal. The authors linked the effect to both weight loss and the direct action of glucagon on the liver.[5]
How does Retatrutide compare with Tirzepatide and Semaglutide?
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Receptors | GLP-1 | GIP + GLP-1 | GIP + GLP-1 + glucagon |
| Dosing in trials | Once weekly | Once weekly | Once weekly |
| Status | Approved | Approved | Phase 3 |
The three molecules form a series: each adds one more receptor. Results from different trials cannot be compared directly, because the populations, durations and analysis methods differ. Head-to-head trials are needed before any conclusion about which is more effective.[6] For comparative laboratory research we also offer Tirzepatide 30 mg.
What doses were used in the trials?
All trials gave Retatrutide once a week under the skin and raised the dose gradually every four weeks. In the phase 2 obesity trial the 12 mg group went 2 → 4 → 8 → 12 mg; the phase 3 programme uses smaller steps of 2 → 4 → 6 → 9 → 12 mg. A lower 2 mg start reduced gastrointestinal side effects compared with starting at 4 mg.[3] For a 20 mg vial dissolved in 2 ml (10 mg/ml), 1 mg corresponds to 0.1 ml; our peptide calculator converts other volumes.
What side effects were reported?
The most common adverse events were gastrointestinal: nausea, diarrhoea, vomiting and constipation. They were mostly mild to moderate and occurred mainly while the dose was being increased. Heart rate rose in a dose-dependent way, peaked around week 24 and then declined. Because the compound is still in trials, long-term safety data are limited.[3][4]
Why is Retatrutide called “GLP-3”?
It is an informal nickname, not a scientific term. There is no hormone called GLP-3; the name simply reflects that Retatrutide acts on three receptors, one more than Tirzepatide.
Is Retatrutide approved?
No. As of 2026 it is still being tested in the phase 3 TRIUMPH programme (obesity and related conditions) and the TRANSCEND programme (type 2 diabetes). It is not approved by the EMA or the FDA and is available only as a research chemical.
How should Retatrutide be stored?
Keep the lyophilized powder dry and dark, long term at −20 °C. Once dissolved, store the solution at 2–8 °C and avoid repeated freezing and thawing. More in our guide How to store peptides.
For laboratory research we offer Retatrutide 20 mg in stock.
Sources
- 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 Metabolism. 2022;34(9):1234–1247. DOI ↗
- 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, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet. 2022;400(10366):1869–1881. DOI ↗
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity – a phase 2 trial. New England Journal of Medicine. 2023;389(6):514–526. DOI ↗
- 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. The Lancet. 2023;402(10401):529–544. DOI ↗
- Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine. 2024;30(7):2037–2048. DOI ↗
- Katsi V, Koutsopoulos G, Fragoulis C, Dimitriadis K, Tsioufis K. Retatrutide – a game changer in obesity pharmacotherapy. Biomolecules. 2025. PMC ↗
The information in this article is for educational purposes only and does not replace medical advice. The substances described are not approved medicines, and Jolt Peptides products are intended solely for laboratory research, not for use in humans or animals.