On September 29, 2026, full results from two of retatrutide's pivotal Phase 3 trials appeared in peer-reviewed journals alongside the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan:
Both trials were presented at an EASD-sponsored retatrutide symposium on September 30. Until now, everything known about retatrutide's Phase 3 program came from Eli Lilly's topline press releases. These publications are the first full, peer-reviewed accounts, with complete methods, statistical analyses and safety data.
The short version: In NEJM, TRIUMPH-1 reports a mean weight loss of 25.0% at 12 mg over 80 weeks vs. 3.9% with placebo, along with significant improvements in knee osteoarthritis pain and sleep apnea severity. In The Lancet, TRIUMPH-2 reports up to 20.8% weight loss and A1C reductions of up to 1.6 points in people with type 2 diabetes. Up to 40% of those participants reached a normal A1C.
TRIUMPH-1 enrolled 2,339 adults at 131 sites in 11 countries. Participants had a BMI of 30 or higher, or a BMI of 27 to under 30 with at least one obesity-related complication, and did not have diabetes. They were randomized 1:1:1:1 to retatrutide 4 mg, 9 mg or 12 mg, or placebo, once weekly for 80 weeks. Overall, 84.7% completed the trial.
| Dose | Mean Weight Change at 80 Weeks | Difference vs. Placebo |
|---|---|---|
| 4 mg | −17.6% | −13.7 points |
| 9 mg | −23.7% | −19.8 points |
| 12 mg | −25.0% | −21.0 points |
| Placebo | −3.9% | — |
Why is this lower than the 28.3% announced in May? The May 2026 topline release reported 28.3% weight loss at 12 mg. The NEJM paper reports 25.0%. Lilly's topline releases have typically led with the efficacy estimand, which estimates the effect if everyone stayed on treatment. Journal primary analyses often use a more conservative approach that counts every randomized participant, including those who stopped the drug. The drug didn't perform worse. The two figures answer slightly different questions, and the lower number is the more realistic expectation across everyone who starts treatment.
TRIUMPH-1 was designed as a "master protocol." Participants with moderate or severe knee osteoarthritis or obstructive sleep apnea were enrolled into two "basket" sub-studies, each with its own primary endpoint tested at the 9 mg and 12 mg doses.
Knee osteoarthritis pain (WOMAC pain score): Pain scores changed by −3.2, −3.5 and −3.6 points on 4, 9 and 12 mg, compared with −1.9 on placebo. The placebo-adjusted differences at 9 and 12 mg were −1.6 and −1.8 points (both P<.001). The result held under the intention-to-treat analysis, with differences of −1.4 and −1.6 points.
Obstructive sleep apnea (apnea-hypopnea index): Breathing interruptions fell by 22.9, 34.3 and 31.7 events per hour on 4, 9 and 12 mg, compared with 9.9 per hour on placebo. The modeled placebo-adjusted differences at 9 and 12 mg were −24.4 and −21.9 events per hour. For context, an AHI of 30 or more is classified as severe sleep apnea, so reductions of this size can move a patient down an entire severity category.
These basket results support Lilly's plan to seek approval for knee osteoarthritis pain and obstructive sleep apnea, as well as obesity.
The authors report that the safety profile was consistent with Phase 2. The most common adverse events were gastrointestinal (nausea, diarrhea, constipation, vomiting), mostly mild to moderate. The paper also flags dose-dependent symptoms of low blood pressure (hypotension), which were more common in participants already taking blood pressure medication. This is worth watching: retatrutide lowers blood pressure substantially, and patients on antihypertensives may need their doses reviewed as they lose weight. For the full picture, see our retatrutide side effects guide.
The authors also argue that retatrutide's effect is large enough to change how obesity is treated: "Given the degree of weight reduction in response to retatrutide, these data support the possibility of treating to a defined target as is done for other diseases (e.g., a glycated hemoglobin target of <6.5% for type 2 diabetes), rather than to a relative percent change in weight."
TRIUMPH-2 randomized 1,152 adults with type 2 diabetes and obesity or overweight to retatrutide 4 mg, 9 mg or 12 mg, or placebo, for 80 weeks. At baseline, participants averaged 234.6 lbs (106.4 kg), a BMI of 38.2 and an A1C of 7.7%.
| Dose | Weight Loss (%) | Weight Loss (lbs) | A1C Change | Reached Normal A1C (<5.7%) |
|---|---|---|---|---|
| 4 mg | 12.7% | 29.8 lbs | −1.4 pts | 28.4% |
| 9 mg | 19.1% | 45.4 lbs | −1.6 pts | 40.0% |
| 12 mg | 20.8% | 49.6 lbs | −1.5 pts | 39.3% |
| Placebo | 4.0% | 9.3 lbs | −0.2 pts | 4.4% |
People with type 2 diabetes typically lose less weight on incretin drugs than people without diabetes, and TRIUMPH-2 fits that pattern. Even so, the numbers are striking. At 12 mg, 59.5% of participants no longer met the BMI criteria for obesity. 67.0% lost at least 15% of their body weight, 52.0% lost at least 20%, and 34.9% lost at least 25%. Participants with a baseline BMI of 35 or higher lost 23.4% (60.8 lbs) on 12 mg. Roughly 4 in 10 participants on the two higher doses reached an A1C below 5.7%, which is in the non-diabetic range.
Cardiovascular risk markers also improved at 12 mg: triglycerides fell 39.5%, non-HDL cholesterol fell 19.6%, systolic blood pressure dropped 10.8 mmHg, waist circumference shrank by 6.7 inches, and hs-CRP (a marker of inflammation) fell 58.3%.
| Adverse Event | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Diarrhea | 27.4% | 33.5% | 33.6% | 13.2% |
| Nausea | 13.7% | 20.8% | 28.0% | 8.0% |
| Constipation | 14.0% | 16.2% | 16.8% | 9.4% |
| Vomiting | 5.5% | 10.2% | 15.7% | 4.2% |
| Dysesthesia | 4.5% | 5.6% | 7.3% | 0.7% |
| Discontinued due to AEs | 3.8% | 11.6% | 7.7% | 4.9% |
Dysesthesia is an abnormal skin sensation, such as tingling or sensitivity to touch. It has been flagged in earlier retatrutide trials, and it shows up again here at up to 7.3% on 12 mg vs. 0.7% on placebo. Most events were mild to moderate and resolved during treatment. More on this in our dysesthesia and tolerability breakdown.
TRIUMPH-3 has not been published yet. It enrolled 1,949 adults with severe obesity (BMI ≥35) and established cardiovascular disease. Its topline results were announced on July 23, 2026: 21.6% weight loss at 9 mg and 22.6% at 12 mg, vs. 3.2% on placebo, with large reductions in triglycerides, blood pressure and hs-CRP. However, the trial did not show a statistically significant reduction in major cardiovascular events. The MACE-3 hazard ratio was 1.12 (95% CI 0.64–1.96), based on a low number of events (27 on retatrutide vs. 23 on placebo). TRIUMPH-3 was not large or long enough to settle the heart-outcome question. That will fall to a dedicated cardiovascular outcomes trial.
Peer-reviewed publication in NEJM and The Lancet is not a regulatory requirement, but it matters. It means independent reviewers have checked the methods and analyses, and it gives physicians the full dataset they will rely on once the drug is available. Lilly has said the TRIUMPH-2 and TRIUMPH-3 results complete the clinical data package for global submissions covering obesity, knee osteoarthritis pain and obstructive sleep apnea. Lilly still plans to file with the FDA in Q1 2027. With a standard review, a decision would be expected around early 2028. See our FDA approval timeline for the scenarios.
Retatrutide is still investigational. It is only legally available through Lilly's clinical trials, so products sold online as "retatrutide" are not the studied drug.
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Join the WaitlistThis article is for educational purposes only and does not constitute medical advice. Retatrutide is an investigational drug and is not FDA approved as of publication. Data are drawn from the TRIUMPH-1 publication in the New England Journal of Medicine, the TRIUMPH-2 publication in The Lancet, and Eli Lilly press releases dated July 23 and September 29, 2026. Consult a qualified healthcare provider before making any treatment decisions.