Retatrutide is an investigational once-weekly injection from Eli Lilly that activates three hormone receptors at once: GIP, GLP-1 and glucagon.[6] In the phase 3 TRIUMPH-1 trial, people on the highest dose lost an average of 28.3% of their body weight over 80 weeks.[2] It is not approved by the FDA, and Lilly says it is legally available only to people taking part in its clinical trials.[2]
This profile covers how retatrutide works, what each trial found, its side effects and where it stands with regulators. For the doses tested in each study, see our retatrutide dosage guide.
What is retatrutide?
Retatrutide is a single synthetic peptide, first known by its research code LY3437943.[6] Lilly is studying it for obesity, type 2 diabetes and weight-related conditions including knee osteoarthritis, sleep apnea and fatty liver disease.[2][8]
Because it is still investigational, there is no approved retatrutide product. Anything sold as retatrutide outside a Lilly trial is not the drug tested in the studies on this page.
How retatrutide works
Retatrutide is a “triple agonist”. It switches on three receptors that normally respond to gut and pancreatic hormones:[6]
- GLP-1 receptor: involved in appetite, fullness and insulin release.
- GIP receptor: a second incretin hormone receptor involved in insulin release.
- Glucagon receptor: involved in energy use by the liver and body.
In laboratory studies in mice, the GLP-1 and GIP activity reduced food intake, and the glucagon activity added an increase in energy expenditure on top of that.[6] For comparison, tirzepatide activates two of these receptors (GIP and GLP-1) and semaglutide activates one (GLP-1).
Retatrutide stays in the body for about 6 days, which is why it is given once a week.[5]
Clinical trial results
Weight loss in TRIUMPH-1 (phase 3)
TRIUMPH-1 enrolled adults with obesity, or overweight plus at least one weight-related condition, who did not have diabetes. Average starting weight was 112.7 kg (248.5 lb).[2]
| Dose | Average weight change at 80 weeks | Lost 30% or more |
|---|---|---|
| 4 mg | −19.0% | 15.3% |
| 9 mg | −25.9% | 37.9% |
| 12 mg | −28.3% | 45.3% |
| Placebo | −2.2% | 0.5% |
In a pre-specified extension for people starting with a BMI of 35 or more, those who stayed on 12 mg reached an average loss of 30.3% at 104 weeks.[2]
Two cautions apply. These are topline results from Lilly and have not yet been published in a peer-reviewed journal. They also use the “efficacy estimand”, which estimates results for people who stayed on treatment; under the stricter treatment-regimen analysis, 12 mg produced 25.0%.[2]
Earlier obesity trial (phase 2)
In the 48-week phase 2 trial of 338 adults, weight fell by 8.7% on 1 mg and up to 24.2% on 12 mg, compared with 2.1% on placebo.[1]
Type 2 diabetes
In the phase 3 TRANSCEND-T2D-1 trial of 537 adults with type 2 diabetes, HbA1c (average blood sugar) fell by 1.69 to 1.94 percentage points after 40 weeks, versus 0.81 with placebo. Body weight fell 11.5% to 15.3%, versus 2.6%. No severe hypoglycemia was reported.[3] An earlier phase 2 diabetes trial found similar results.[4]
Liver fat
In a substudy of people with metabolic dysfunction-associated steatotic liver disease, liver fat fell by 81.4% on 8 mg and 82.4% on 12 mg after 24 weeks. Most people on those doses reached normal liver fat levels.[7]
Side effects
The most common side effects in TRIUMPH-1 were gastrointestinal, and they rose with dose:[2]
| Side effect | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Nausea | 28.6% | 38.4% | 42.4% | 14.8% |
| Diarrhea | 25.2% | 34.1% | 32.0% | 13.5% |
| Constipation | 23.8% | 25.9% | 26.1% | 10.9% |
| Vomiting | 10.6% | 22.8% | 25.3% | 4.8% |
- Dysesthesia (an abnormal skin sensation such as tingling) was reported by 5.1% to 12.5% of people on retatrutide versus 0.9% on placebo. Most cases were mild to moderate and resolved during treatment.[2]
- Stopping because of side effects happened in 4.1%, 6.9% and 11.3% of people on 4, 9 and 12 mg, versus 4.9% on placebo.[2]
- Heart rate rose with dose in the phase 2 trial, peaked at 24 weeks and then declined.[1]
- Starting low helped: a 2 mg starting dose partly reduced gastrointestinal side effects compared with starting at 4 mg.[1]
Doses studied
Phase 3 trials tested 4 mg, 9 mg and 12 mg once a week, reached by increasing the dose in steps; 4 mg needed only one step up.[2][3] Phase 2 trials tested 0.5 mg to 12 mg.[1][4] These are research doses, not prescribing guidance. Our dosage guide breaks down each trial.
FDA status and what’s next
Retatrutide has not been approved by the FDA.[2] The TRIUMPH program includes four phase 3 trials in more than 5,800 people, covering obesity, sleep apnea, knee osteoarthritis and cardiovascular disease.[8] Lilly said results from TRIUMPH-2 (people with type 2 diabetes) and TRIUMPH-3 (people with cardiovascular disease) would follow later in 2026.[2]
We update this profile as new results and regulatory decisions are published. Subscribe below to get them in your inbox.
Retatrutide vs tirzepatide and semaglutide
Retatrutide’s reported weight loss is numerically larger than in the main tirzepatide and semaglutide obesity trials, but comparing separate trials is unreliable: the people enrolled, the trial lengths and the analysis methods all differ. See our tirzepatide and semaglutide profiles for each drug’s own evidence.