A triple hormone receptor agonist
Retatrutide is a single peptide with a fatty-acid chain attached, which keeps it in the body longer. It activates three receptors:[1]
- GLP-1 receptors, the target of semaglutide. GLP-1 signals reduce appetite and slow stomach emptying.
- GIP receptors, which tirzepatide also targets alongside GLP-1.
- Glucagon receptors, the third target, which neither semaglutide nor tirzepatide acts on.
Compared with the body's own hormones, retatrutide is more potent at the GIP receptor and less potent at the glucagon and GLP-1 receptors.[1] The potency figures and each receptor's role are on the retatrutide mechanism of action page.
LY3437943: retatrutide's code name
LY3437943 is Eli Lilly's development code for retatrutide. Early papers and registry records use the code, and later ones the generic name, so ClinicalTrials.gov titles often show both, as in "Retatrutide (LY3437943)".[2][4]
Is retatrutide a "GLP-3"?
No. "GLP-3" is an online nickname, not a scientific name. The body makes GLP-1 and GLP-2, but no hormone called GLP-3 is known. People use the label because retatrutide came after GLP-1 drugs such as semaglutide and dual GIP/GLP-1 drugs such as tirzepatide, and acts on a third receptor. Its accurate description is a GIP, GLP-1 and glucagon receptor triple agonist.[1]
| Drug | Receptors | Nickname you may see |
|---|---|---|
| Semaglutide | GLP-1 | "GLP-1" |
| Tirzepatide | GIP + GLP-1 | "Dual agonist" |
| Retatrutide | GIP + GLP-1 + glucagon | "Triple agonist", "GLP-3" |
What does retatrutide do in the body?
Retatrutide lowers body weight and blood sugar, and in trials it also improved sleep apnea and knee pain. These are the measured effects, with the trial each comes from:
| Effect | Size of the effect | Trial |
|---|---|---|
| Body weight | −25.0% on 12 mg vs −3.9% on placebo, 80 weeks[5] | TRIUMPH-1 |
| Blood sugar (HbA1c) | Up to −2.02 points vs −0.01 on placebo, 24 weeks[3] | Phase 2, type 2 diabetes |
| Sleep apnea (breathing pauses per hour) | −31.7 to −34.3 on 9–12 mg vs −9.9 on placebo[8] | TRIUMPH-1-OSA, 80 weeks |
| Knee pain (WOMAC) | Down by up to 4.3 points (73.1%) from a baseline of 6.0[7] | TRIUMPH-1 knee substudy |
| Heart rate | Rose with dose, peaked around week 24, then declined[1] | Phase 2 obesity |
How much weight people lost at each dose is on the results page.
Half-life and weekly dosing
Its half-life is about 6 days.[2][1] That means half of a dose is still in the body about six days later, which is why one injection a week is enough. In every trial it was given once weekly by injection under the skin.[1] The week-by-week math is on the retatrutide half-life page.
The trial program
| Trial | Who | Status (Nov 2026) |
|---|---|---|
| TRIUMPH-1 | Obesity without diabetes, 2,339 people | Completed, published |
| TRIUMPH-2 | Obesity with type 2 diabetes | Completed, published |
| TRIUMPH-3 | BMI ≥35 with heart disease | Completed, topline only |
| TRIUMPH-4 | Obesity with knee osteoarthritis | Completed, published |
| TRIUMPH-5 | Head-to-head vs tirzepatide | Active; primary completion estimated Nov 2026, no results yet |
| TRANSCEND-T2D-2 | Type 2 diabetes vs semaglutide 2 mg | Topline reported |
| TRIUMPH-Outcomes | Heart and kidney outcomes, ~10,000 people | Active |
Statuses are from ClinicalTrials.gov and Lilly announcements.[4][6] All 33 registered studies are listed in the retatrutide clinical trials tracker.
What it is being studied for
The trial program goes well beyond weight loss. Registered retatrutide trials study:[4]
- Obesity, with and without type 2 diabetes (TRIUMPH-1 and TRIUMPH-2)
- Type 2 diabetes blood-sugar control (TRANSCEND-T2D-1 to -3, including kidney impairment)
- Knee osteoarthritis pain (TRIUMPH-4) and obstructive sleep apnea (substudies of TRIUMPH-1 and -2)
- People with established heart disease (TRIUMPH-3) and long-term heart and kidney outcomes (TRIUMPH-Outcomes)
- Keeping weight off (TRIUMPH-6) and chronic low back pain (TRIUMPH-7)
The results so far, dose by dose, are on the results page, and the reported side effects are on the side effects page.
How it got here
| Stage | What was published |
|---|---|
| Phase 1b | Tested in type 2 diabetes; half-life about 6 days (Lancet, 2022)[2] |
| Phase 2 | Obesity trial in 338 adults and type 2 diabetes trial in 281 people (NEJM and Lancet, 2023)[1][3] |
| Phase 3 | TRIUMPH-1 published in NEJM, September 2026, plus several other completed trials[5] |
| Next | U.S. submission planned for the first quarter of 2027[6] |
Is it approved?
No. It is investigational and not approved anywhere. Lilly plans to submit it to the FDA in early 2027. See FDA approval status.[6]
Related
Frequently asked questions
Is retatrutide a peptide?
Yes. It is a single peptide modified with a fatty-acid chain to extend how long it lasts in the body.[1]
Why is retatrutide called GLP-3?
It is an informal nickname. Retatrutide acts on a third receptor (glucagon) on top of the GLP-1 and GIP receptors, but there is no hormone called GLP-3.
What does "triple agonist" mean?
It activates three different hormone receptors (GIP, GLP-1 and glucagon). Semaglutide activates one, and tirzepatide activates two.
Sources
- Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial
- Urva S et al. LY3437943, a GIP, GLP-1 and glucagon receptor agonist, in type 2 diabetes: phase 1b
- Rosenstock J et al. Retatrutide in people with type 2 diabetes: a phase 2 trial
- Retatrutide studies (NCT04881760, NCT05929066, NCT05931367, NCT06662383, NCT07629401 and others)
- Jastreboff AM et al. Retatrutide for obesity (TRIUMPH-1)
- Lilly: retatrutide vs semaglutide 2 mg in TRANSCEND-T2D-2
- Lilly: retatrutide results presented at ADA 2026
- Grunstein RR et al. Retatrutide for obstructive sleep apnea (TRIUMPH-1-OSA, TRIUMPH-2-OSA)