At a glance: Retatrutide is an investigational once-weekly injection from Eli Lilly that activates three hormone receptors at once: GIP, GLP-1 and glucagon. In the phase 3 TRIUMPH-1 trial, people on the highest dose lost an average of 28.3% of body weight over 80 weeks, versus 2.2% on placebo, among the largest losses seen with any obesity drug. It is not approved anywhere. Lilly plans to file with FDA in early 2027. FDA says it cannot legally be compounded, and Lilly warns against any retatrutide sold outside its clinical trials.
What is retatrutide?
Retatrutide (development code LY3437943) is a lab-made peptide developed by Eli Lilly, the maker of tirzepatide (Mounjaro and Zepbound). It is a single molecule that acts on three hormone receptors, which is why Lilly calls it a "triple agonist." Media sometimes call it "GLP-3," but Lilly notes that is not an accurate name.
It is being studied for obesity, type 2 diabetes, knee osteoarthritis pain, sleep apnea, chronic low back pain, heart and kidney outcomes and fatty liver disease (MASLD).
How does retatrutide work?
- GLP-1 receptor: reduces appetite, slows stomach emptying and boosts insulin after meals, the same target as semaglutide (Wegovy)
- GIP receptor: another gut hormone that helps regulate insulin and appetite, the second target of tirzepatide
- Glucagon receptor: the new addition. Glucagon signaling is thought to increase energy use and help burn fat, including liver fat
- Combined effect: adding glucagon activity on top of GLP-1 and GIP is believed to explain its unusually large weight loss
What the research shows so far
| Trial | Who was studied | Main finding |
|---|---|---|
| Phase 2 (NEJM, 2023) | 338 adults with obesity or overweight, 48 weeks | Up to 24.2% average weight loss vs 2.1% on placebo |
| TRIUMPH-4 (Dec 2025) | 445 adults with obesity and knee osteoarthritis, 68 weeks | Up to 28.7% weight loss vs 2.1%; knee pain scores fell about 75% vs 40% on placebo |
| TRIUMPH-1 (May 2026) | 2,339 adults with obesity or overweight plus a weight-related condition, no diabetes, 80 weeks | 19.0%, 25.9% and 28.3% weight loss across three doses vs 2.2% on placebo; 45% on the top dose lost at least 30% |
| TRIUMPH-2 (July 2026) | 1,152 adults with type 2 diabetes and obesity or overweight, 80 weeks | Up to 20.8% weight loss vs 4.0%; A1C fell up to 1.6 points vs 0.2 |
| TRIUMPH-3 (July 2026) | 1,949 adults with severe obesity and heart disease, 80 weeks | Up to 22.6% weight loss vs 3.2%; heart events not significantly different from placebo |
Weight-loss figures are Lilly's "efficacy estimand," which reflects people who stayed on treatment. Results counting everyone who started are somewhat lower. Most phase 3 results so far come from company announcements and meeting presentations.
Why it gets attention
- Bariatric-surgery-level weight loss: nearly half of top-dose TRIUMPH-1 participants lost 30% or more of their body weight
- Next after Zepbound: seen as Lilly's successor to tirzepatide, with a third hormone target
- Related conditions: improvements in knee pain, blood sugar and sleep apnea in trial subgroups
- A booming gray market: "research" retatrutide is widely sold online and in clinics, years before any approval
How it is used
In trials, retatrutide is given as a once-weekly injection under the skin, starting low and increasing gradually to reduce stomach side effects. It is available only through Lilly-sponsored clinical trials. Because it is not approved, there is no approved dose, and this page does not provide dosing guidance.
What about side effects?
From Lilly's TRIUMPH trial reports, side effects were mostly digestive and dose-related:
- Nausea, diarrhea, constipation and vomiting: the most common. In TRIUMPH-1, nausea affected about 29% to 42% of retatrutide users vs 15% on placebo, and vomiting up to 25% vs 5%. Most cases were mild to moderate.
- Dysesthesia: unusual skin sensations such as tingling, burning or sensitivity, a side effect not typical of other GLP-1 drugs. It affected about 5% to 13% in TRIUMPH-1 and up to 21% on the top dose in TRIUMPH-4, vs about 1% on placebo. It was usually mild, and most people kept taking the drug.
- Stopping treatment: 4% to 11% of TRIUMPH-1 participants quit due to side effects (vs 5% on placebo), and up to 18% on the top dose in TRIUMPH-4, partly from losing too much weight.
- Loss of appetite, plus slightly more urinary and upper respiratory infections than placebo.
Long-term safety is still being studied. Risks seen with related drugs, such as gallbladder and pancreas problems, muscle loss with rapid weight loss, and pregnancy concerns, remain open questions.
Regulatory status
- Not approved by FDA or any other regulator.
- Lilly said in July 2026 that it plans to submit an application to FDA in the first quarter of 2027. Approval would follow FDA review.
- FDA says retatrutide cannot be used in compounding under federal law, because it is not part of any approved drug.
- Lilly states that no one should take anything claiming to be retatrutide outside its clinical trials. Black-market products may contain the wrong dose, the wrong ingredient or contaminants. A 2026 preprint (not yet peer reviewed) found people using unapproved retatrutide lost about half as much weight at one year as trial participants.
Retatrutide vs other obesity drugs
| Semaglutide (Wegovy) | Tirzepatide (Zepbound) | Retatrutide | |
|---|---|---|---|
| Hormone targets | GLP-1 | GIP + GLP-1 | GIP + GLP-1 + glucagon |
| Status | FDA-approved | FDA-approved | Investigational (phase 3) |
| Distinctive side effect | Digestive | Digestive | Digestive, plus skin-sensation changes (dysesthesia) |
The bottom line
Retatrutide has produced some of the largest weight losses ever recorded in obesity trials, along with better blood sugar and less knee pain in people who need it. But it is still investigational, side effects cause a meaningful share of people to stop, long-term safety is unknown, and the earliest possible FDA filing is 2027. Products sold now as retatrutide are unapproved and unverified. Anyone seeking weight-loss treatment should talk with a clinician about approved options or legitimate clinical trials.
Frequently asked questions
What is Retatrutide?
A once-weekly injection from Eli Lilly that acts on three hormone receptors at once: GLP-1, GIP and glucagon. It is still investigational and not approved anywhere.
How is Retatrutide taken?
Weekly subcutaneous injection (trials).
Is Retatrutide FDA approved?
Investigational; Lilly plans to file with the FDA in Q1 2027.
That means no regulator has reviewed its safety, effectiveness or manufacturing quality for this use.
What has research shown about Retatrutide?
- Weight loss in adults with obesity or overweight: up to 28% average loss at 80 weeks in the phase 3 TRIUMPH-1 trial.
- Weight and blood sugar in adults with type 2 diabetes (TRIUMPH-2).
- Heart-risk factors in adults with heart disease (TRIUMPH-3).
What side effects have been reported?
- Nausea (about 4 in 10 on 12 mg)
- Diarrhoea (about 1 in 3)
- Constipation (about 1 in 4)
- Vomiting (about 1 in 4)
- Tingling, burning or oversensitive skin — dysesthesia (about 1 in 8)
- Urinary tract infection
Serious or less common risks are listed in the Side Effects section above.
What is still unknown about its safety?
Most of it. Retatrutide has not been through the trials that establish long-term safety in people, and products sold online are made by unregulated labs. Independent testing of online peptides has repeatedly found contents that do not match the label.
References
- Eli Lilly: What to know about retatrutide. View source
- Eli Lilly: Retatrutide delivered powerful weight loss in pivotal phase 3 obesity trial (TRIUMPH-1, May 2026). View source
- Eli Lilly: Retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3, July 2026). View source
- Eli Lilly: Retatrutide delivered weight loss of up to 71.2 lbs with osteoarthritis pain relief (TRIUMPH-4, December 2025). View source
- Patient Care: Retatrutide associated with weight loss of up to 24% in 48-week phase 2 trial (Jastreboff et al., NEJM 2023). View source
- Alliance for Pharmacy Compounding: Don't compound with retatrutide (quoting FDA). View source
- Accelerating use of unapproved retatrutide is associated with weaker weight loss (preprint, 2026). View source