Eli Lilly's TRIUMPH-2 trial tested retatrutide, its weekly triple agonist, in adults with obesity or overweight and type 2 diabetes. Published in The Lancet on 29 September 2026 and presented at the EASD meeting in Milan, it found 20.8% average weight loss at 80 weeks on the 12 mg dose for people who stayed on treatment, and 18.8% counting everyone, against 5.1% on placebo.
What happened
TRIUMPH-2 (PubMed 42810372) randomised 1,152 adults at 92 centres in eight countries. Everyone had type 2 diabetes with an A1C between 6.5% and 10.5%, managed by diet and exercise or up to three oral medicines, and a BMI of 27 or more. At the start, average BMI was 38.2, average A1C was 7.7%, and 92% were taking an oral diabetes medicine, including sulfonylureas in some cases. They were assigned in equal groups to retatrutide 4 mg, 9 mg or 12 mg, or placebo, once a week for 80 weeks. 84% completed treatment. Lilly funded the trial.
| Placebo | 4 mg | 9 mg | 12 mg | |
|---|---|---|---|---|
| Weight lost, counting everyone (Lancet) | 5.1% | 11.9% | 16.8% | 18.8% |
| Weight lost, if all stayed on treatment (Lilly) | 4.0% | 12.7% | 19.1% | 20.8% |
| A1C fall from 7.7% (Lilly) | 0.2 | 1.4 | 1.6 | 1.5 |
| Reached A1C below 5.7% (Lilly) | 4.4% | 28.4% | 40.0% | 39.3% |
| Lost 20% or more (Lilly) | 1.5% | 24.0% | 45.3% | 52.0% |
On the 12 mg dose, Lilly reports triglycerides down 39.5%, systolic blood pressure down 10.8 mmHg, waist down 16.9 cm and the inflammation marker hs-CRP down 58.3%. People who started at a BMI of 35 or more lost 23.4% on 12 mg.
What were the side effects?
Mostly gut. Diarrhoea affected 27% to 34% on retatrutide against 13% on placebo, and nausea 14% to 28% against 8%, rising with dose. Low blood pressure was reported in up to 6% on retatrutide against under 1% on placebo, and dysesthesia, an unusual skin sensation, in up to 7% against 1%. Stopping because of a side effect or death was 4% on 4 mg, 12% on 9 mg and 8% on 12 mg, against 5% on placebo. Seven people died across the trial; investigators judged none of the deaths related to the study drug.
What it does not tell us
- How it compares with tirzepatide or semaglutide. The comparison was placebo only.
- How much of the loss was muscle. The abstract does not report body composition.
- Whether it lowers heart attacks or kidney disease. Better blood fats and blood pressure are encouraging, but they are not the same as fewer events.
- What happens after 80 weeks or after stopping.
The same doses in people without diabetes, in TRIUMPH-1, gave 25.0% counting everyone. They are separate trials with different people, so treat the gap as a rough guide rather than a direct comparison.
What it means for you
If you have type 2 diabetes and take semaglutide or tirzepatide, this is a result to watch, not one to act on. Retatrutide is not approved for any use as of October 2026, and Lilly has said it plans to file in the US in the first quarter of 2027. If you take a sulfonylurea or insulin alongside any of these drugs, falling blood sugar is the thing to plan for with your prescriber as your weight and appetite drop.
Low blood pressure was more common on retatrutide too. If you take blood pressure tablets and feel dizzy on standing, tell your doctor rather than adjusting anything yourself. For how the triple agonist differs from the drug many readers already take, see retatrutide against tirzepatide.
What to do with this
When appetite drops this far, each meal you do eat has to carry more of the day's protein and fibre, so build every plate around them first.