Retatrutide trials so far show large average weight loss and blood sugar drops at the higher doses, but the reports have real limits. They ran 36 to 80 weeks, each report was funded or released by Eli Lilly, and dropout rates did not rise in a straight line with dose. Lilly describes retatrutide as investigational, so none of these results is a result for an approved medicine.
What did the retatrutide trials measure?
Retatrutide is a once-weekly investigational medicine that activates three hormone receptors: GIP, GLP-1 and glucagon. Lilly’s September 29, 2026 release says it is an investigational molecule that cannot be legally sold or marketed for human use. Four reports are the basis for the results below:
- a 2023 Phase 2 obesity trial published in the New England Journal of Medicine,
- a 2025 Phase 2 body-composition substudy in adults with type 2 diabetes,
- TRANSCEND-T2D-1, a 2026 Phase 3 trial in adults with type 2 diabetes,
- TRIUMPH-2, a Phase 3 trial whose results Lilly released on September 29, 2026.
| Trial | Who was in it | Length | Doses | Main result as reported |
|---|---|---|---|---|
| 2023 Phase 2 obesity trial | 338 adults with obesity, or overweight plus a weight-related condition | 48 weeks | 1 mg, 4 mg, 8 mg, 12 mg | Weight change at 48 weeks: −8.7% (1 mg), −17.1% (combined 4 mg), −22.8% (combined 8 mg), −24.2% (12 mg); placebo −2.1% |
| 2025 body-composition substudy | 189 adults with type 2 diabetes | Fat mass measured at week 36 | 0.5 mg, 4 mg, 8 mg, 12 mg; dulaglutide 1.5 mg | Change in total fat mass versus placebo: −10.7 (4 mg pooled), −21.6 (8 mg pooled), −18.7 (12 mg); the 0.5 mg change was not significant |
| TRANSCEND-T2D-1 (2026 Phase 3) | 537 adults with type 2 diabetes not controlled by diet and exercise alone | 40 weeks | 4 mg, 9 mg, 12 mg; placebo | Body weight: −11.5% (4 mg), −13.9% (9 mg), −15.3% (12 mg), versus −2.6% on placebo. HbA1c: −1.69%, −1.86%, −1.94%, versus −0.81% on placebo |
| TRIUMPH-2 (Lilly release, September 29, 2026) | 1,152 randomized adults with type 2 diabetes and obesity or overweight | 80 weeks | 4 mg, 9 mg, 12 mg; placebo | Body weight: −12.7% (4 mg), −19.1% (9 mg), −20.8% (12 mg), versus −4.0% on placebo. A1C: −1.4%, −1.6%, −1.5%, versus −0.2% on placebo |
Each of these compares retatrutide with placebo. The only exception is the body-composition substudy, which also had a dulaglutide arm. None of these reports compares retatrutide with semaglutide (Ozempic).
How do the doses compare?
Within each trial, the higher doses produced more weight loss than the lower doses. In the 2023 obesity trial, average weight loss at 48 weeks was 8.7% on 1 mg and 24.2% on 12 mg, against 2.1% on placebo. In TRIUMPH-2, weight loss at 80 weeks rose from 12.7% on 4 mg to 19.1% on 9 mg and 20.8% on 12 mg, against 4.0% on placebo, according to Lilly’s release.
Do not line these numbers up across trials. The 2023 trial enrolled adults with obesity, TRIUMPH-2 enrolled adults with type 2 diabetes and obesity or overweight, and TRANSCEND-T2D-1 enrolled adults with diabetes whose blood sugar was not controlled by diet and exercise alone. A 24.2% figure from one group and a 20.8% figure from another are not a fair ranking. The fair comparison is each dose against placebo inside the same trial.
The largest number in a headline is usually the top dose. Look at the lower arms in the table too, since they show what a smaller dose did in the same group.
How long did the studies last?
The trials ran 36 weeks for the body-composition substudy, 40 weeks for TRANSCEND-T2D-1, 48 weeks for the 2023 obesity trial, and 80 weeks for TRIUMPH-2, followed by 4 more weeks of follow-up. TRIUMPH-2 is the longest in this set. Results at 40 or 48 weeks do not tell you what happens after those points.
The TRIUMPH-2 figures are labeled as the efficacy estimand. Lilly defines that as the result if all randomized participants had stayed on the study drug for 80 weeks without starting prohibited weight-management treatment. That is a useful yardstick, but it is not a record of what every participant experienced. The TRANSCEND-T2D-1 HbA1c result is labeled as the treatment-regimen estimand.
How many people stopped early, and what side effects did they have?
Stopping because of side effects is one of the clearest limits in the trial data. In TRIUMPH-2, 3.8% of people on 4 mg, 11.6% on 9 mg and 7.7% on 12 mg stopped because of side effects, compared with 4.9% on placebo. In TRANSCEND-T2D-1, stopping because of side effects was 2% to 5% on retatrutide and 0% on placebo. The 9 mg dropout rate was higher than the 12 mg rate, so dropouts did not rise steadily with dose.
| Group in TRIUMPH-2 | Stopped due to side effects | Diarrhea | Nausea | Vomiting | Dysesthesia |
|---|---|---|---|---|---|
| Retatrutide 4 mg | 3.8% | 27.4% | 13.7% | 5.5% | 4.5% |
| Retatrutide 9 mg | 11.6% | 33.5% | 20.8% | 10.2% | 5.6% |
| Retatrutide 12 mg | 7.7% | 33.6% | 28.0% | 15.7% | 7.3% |
| Placebo | 4.9% | 13.2% | 8.0% | 4.2% | 0.7% |
Lilly’s release describes these side effects as generally mild to moderate, with most resolving during treatment. The release uses the term dysesthesia without defining it, so read the full paper for what it covers. In the 2023 obesity trial, the most common side effects were gastrointestinal, and they were partly reduced with a lower starting dose (2 mg rather than 4 mg). Heart rate rose with dose, peaking at 24 weeks and declining after that. TRANSCEND-T2D-1 reported two deaths, both in the 4 mg group, which the paper says were unrelated to the study drug.
Why do the first announcements need a full review?
A press release is the maker’s account of its own trial. Lilly’s TRIUMPH-2 release says the results were presented at the European Association for the Study of Diabetes meeting and published in The Lancet at the same time. The published paper is where the full tables, denominators and definitions live, so read that before repeating a headline number.
- Funding. Eli Lilly funded the 2023 trial, the 2025 substudy and TRANSCEND-T2D-1, and it makes retatrutide.
- Copies online. One copy of Lilly’s release, on pr.midvalejournal.com, is marked as a paid placement. Check which version you are reading.
- Subgroups. Lilly reports that people with a starting BMI of 35 or higher on 12 mg lost an average of 23.4%. That is one subgroup, not the whole trial.
- Footnotes. Lilly’s release marks some secondary results as not controlled for family-wise type 1 error. Treat those numbers as less firm than the primary results.
- Who was studied. In the 2025 substudy, 189 people were enrolled, 103 completed both scans, and 85% of participants were White. Its authors describe the lean-mass finding as their interpretation of the data.
- Headlines. A USA Today story dated October 28, 2026 is headlined “Retatrutide beats Ozempic on weight loss, blood sugar control, study says.” The trials above compare retatrutide with placebo or, in one substudy, dulaglutide. Check which study a headline is describing before you accept any comparison with Ozempic.
What is still unknown?
As of October 2026, Lilly says it plans to submit a Biologics License Application to the U.S. Food and Drug Administration in the first quarter of 2027. Until a regulator decides, retatrutide is not an approved medicine. Lilly also says further results from the obstructive sleep apnea trial within TRIUMPH-2 will be presented later, and that more of its Phase 3 results are expected over the next year.
Long-term safety is the big open question. For the GLP-1 drug class in general, the National Academy of Medicine’s GLP-1 health basics page says long-term studies show sustained benefits and no significant safety concerns, while researchers continue to monitor effects on muscle mass, bone health and mental well-being. That statement covers the class, not retatrutide specifically.
What to check before you read more
- Read the full papers: the 2023 obesity trial and TRANSCEND-T2D-1, not just summaries. Find the arm-by-arm tables and the stopped-treatment counts.
- Note which estimand each percentage uses before comparing two numbers.
- Match the population in the trial to your own situation. A diabetes result and an obesity result are not interchangeable.
- Look up the trial registry numbers the reports cite: NCT05929079 (TRIUMPH-2), NCT06354660 (TRANSCEND-T2D-1), NCT04881760 (2023 obesity trial) and NCT04867785 (body-composition substudy).
- If you take a GLP-1 medicine now, bring these results to your clinician rather than changing anything on your own.
By Sense and Evidence Health Research Team