The complete guide
Retatrutide: what it is, what the trials show, and where it stands in the US
Retatrutide is Eli Lilly’s once-weekly triple hormone receptor agonist. It produced the largest average weight loss yet reported in obesity trials — and it is still not approved by the FDA. Here is the evidence, with every figure linked to its source.
By the RetaRadar editors · Published October 1, 2026
What retatrutide is
Retatrutide (development code LY3437943) is a single synthetic peptide that activates three hormone receptors at once: GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1) and glucagon. That is why it is called a “triple agonist” or “triple G”. It was designed by Eli Lilly and is given as a once-weekly injection under the skin; in early studies its half-life was about six days.
It is a step beyond the two drugs most Americans know. Semaglutide (Ozempic, Wegovy) acts on GLP-1 alone. Tirzepatide (Mounjaro, Zepbound) acts on GLP-1 and GIP. Retatrutide adds glucagon.
How it works
- GLP-1 slows stomach emptying, increases insulin release after meals and acts on brain areas that control appetite.
- GIP also boosts insulin release and appears to add to the appetite and weight effects of GLP-1, as seen with tirzepatide.
- Glucagon is the unusual part. On its own it raises blood sugar, but it also increases energy expenditure and fat breakdown in the liver. Paired with GLP-1 and GIP, which control blood sugar, the aim is extra weight and liver-fat loss without the glucose penalty.
The liver effect showed up clearly in a phase 2 substudy in Nature Medicine: after 24 weeks, liver fat fell by an average of 82.4% on the 12 mg dose, and 86% of people on that dose reached a normal liver-fat level, against 0% on placebo (Sanyal et al., Nat Med 2024).
Development history
| Year | Milestone |
|---|---|
| 2019 | First-in-human single-dose study in healthy volunteers (NCT03841630). |
| 2022 | Lilly scientists publish the molecule’s design and early data in Cell Metabolism (Coskun et al.). Phase 1b in type 2 diabetes appears in The Lancet (Urva et al.). |
| 2023 | Phase 2 obesity trial in the New England Journal of Medicine and phase 2 diabetes trial in The Lancet, both in June. |
| 2023–24 | The TRIUMPH (obesity) and TRANSCEND-T2D (diabetes) phase 3 programs start. |
| Dec 2025 | First phase 3 readout: TRIUMPH-4 in obesity with knee osteoarthritis. |
| 2026 | TRANSCEND-T2D-1, TRIUMPH-1, -2 and -3 report. Full TRIUMPH-1 and TRIUMPH-2 papers published September 29, 2026. Lilly plans its FDA submission for Q1 2027. |
Phase 2 results
Obesity (NEJM, 2023)
The trial enrolled 338 adults with obesity, or overweight plus a weight-related condition, without diabetes. After 48 weeks the average weight change was −8.7% on 1 mg, −17.1% on 4 mg, −22.8% on 8 mg and −24.2% on 12 mg, against −2.1% on placebo. On 12 mg, every participant lost at least 5% of body weight and 83% lost at least 15% (Jastreboff et al., NEJM 2023).
Type 2 diabetes (Lancet, 2023)
In 281 adults with type 2 diabetes, HbA1c fell by up to 2.02 percentage points at 24 weeks on 12 mg, compared with 1.41 points on dulaglutide 1.5 mg and almost no change on placebo. Body weight fell by up to 16.9% at 36 weeks (Rosenstock et al., Lancet 2023).
The TRIUMPH phase 3 program
Lilly’s phase 3 program has more than a dozen trials registered on ClinicalTrials.gov. The ones that have reported so far:
| Trial | Who | Length | Weight change, top dose | Reported |
|---|---|---|---|---|
| TRIUMPH-4 | Obesity + knee osteoarthritis (445) | 68 wk | −28.7% (12 mg) vs −2.1% | Dec 11, 2025 |
| TRANSCEND-T2D-1 | Type 2 diabetes (537) | 40 wk | −16.8% (12 mg); HbA1c up to −2.0 points | 2026; full paper June 2026 |
| TRIUMPH-1 | Obesity without diabetes (2,339) | 80 wk | −28.3% (12 mg) vs −2.2% | May 21, 2026 |
| TRIUMPH-2 | Obesity + type 2 diabetes (1,152) | 80 wk | −20.8% (12 mg) vs −4.0% | Jul 23, 2026 |
| TRIUMPH-3 | Severe obesity + heart disease (1,949) | 80 wk | −22.6% (12 mg) vs −3.2% | Jul 23, 2026 |
Figures are Lilly’s “efficacy estimand” (people who stayed on treatment), from its press releases: TRIUMPH-4, TRIUMPH-1, TRIUMPH-2 and -3, TRANSCEND-T2D-1 (Lancet).
Two ways of counting
Headlines and journal papers often quote different numbers for the same trial. Lilly’s releases lead with the efficacy estimand, which reflects people who kept taking the drug. Journals usually lead with the treatment-regimen estimand, which counts everyone randomized, including those who stopped. For TRIUMPH-1, the NEJM paper published on September 29, 2026 reports −25.0% at 80 weeks on 12 mg by that stricter method, against −3.9% on placebo (Jastreboff et al., NEJM 2026). The Lancet paper on TRIUMPH-2 gives −18.8% versus −5.1% (Lancet 2026).
Beyond weight
- Longer treatment: in a 104-week extension of TRIUMPH-1 in people with a BMI of 35 or more, the 12 mg group averaged −30.3% (Lilly, efficacy estimand).
- Knee pain: in TRIUMPH-4, WOMAC pain scores fell by about three quarters on retatrutide, against 40% on placebo.
- Sleep apnea: in a TRIUMPH-1 substudy, breathing interruptions fell by about 32 to 34 events per hour (treatment-regimen) versus about 10 on placebo.
- Blood sugar: in TRIUMPH-2, up to 40% of people with type 2 diabetes reached an HbA1c below 5.7%, the normal range.
Still to come
TRIUMPH-5 compares retatrutide head-to-head with tirzepatide (primary completion expected November 2026). TRANSCEND-T2D-2 compares it with semaglutide in type 2 diabetes. A 10,000-person cardiovascular and kidney outcomes trial, TRIUMPH-OUTCOMES, runs to 2029 (NCT06383390).
Side effects
Side effects were similar in kind to other incretin drugs. The most common were nausea, vomiting, diarrhea and constipation, mostly while the dose was being increased. In TRIUMPH-1, nausea affected 28.6% to 42.4% of people on retatrutide against 14.8% on placebo.
Two findings stand out. First, dysesthesia — abnormal or unpleasant skin sensations — appeared in every phase 3 trial, most of all in TRIUMPH-4, where it affected 20.9% of people on 12 mg against 0.7% on placebo. Second, more people stopped treatment on the highest dose: 18.2% on 12 mg in TRIUMPH-4 because of side effects, against 4.0% on placebo. Phase 2 also found a dose-related rise in heart rate, and the TRIUMPH-2 paper reports hypotension in up to 6% on 12 mg. These figures come from controlled trials with medical supervision; they say nothing about unregulated products.
FDA status in the US
- Not approved. Retatrutide is not approved by the FDA for any condition. In its July 23, 2026 trial release and its second-quarter results, Lilly said the clinical package is complete and that it plans to submit to the FDA in the first quarter of 2027 (Lilly Q2 2026 results, SEC filing).
- Cannot be compounded. The FDA states that retatrutide “cannot be used in compounding under federal law”. It also warns about products labeled “for research purposes” or “not for human consumption” that are in practice sold to consumers (FDA’s concerns with unapproved GLP-1 drugs used for weight loss).
- Warning letters. The FDA has sent warning letters naming retatrutide to online peptide sellers, including Summit Research Peptides (December 10, 2024), ASN-LABS (September 9, 2025) and Gram Peptides (March 31, 2026). The letters say a “research use only” label does not change how the FDA treats a product that is marketed for people.
- Expanded access. ClinicalTrials.gov lists a pre-approval expanded access program run by Lilly (NCT07629401). Access goes through a treating physician, not through online stores.
For approved alternatives and what they cost, see Zepbound vs Wegovy: cost and insurance coverage. For the risks of counterfeit and compounded products, read fake and compounded GLP-1 drugs.
Research-grade sellers
Retatrutide is sold online by chemical suppliers as a research compound, for laboratory use only and not for human consumption. Quality varies widely: some sellers publish independent lab reports for every batch, others publish nothing or reuse other shops’ reports. We check US-facing sellers against a published checklist and rank them on our retatrutide vendor rankings.
Our sponsored partner, LeoLab, lists retatrutide for sale in several vial sizes with third-party lab reports; see our LeoLab review for the full record. LeoLab pays for its position (disclosure). Nothing here is a recommendation to use retatrutide; if you are considering treatment for weight or diabetes, talk to a licensed clinician about FDA-approved options.