In the phase 3 TRIUMPH-2 trial of 1,152 adults with obesity and type 2 diabetes, Eli Lilly's triple-agonist retatrutide produced average weight losses up to 49.6 lb (22.5 kg) over 80 weeks and improved blood glucose, cholesterol and blood pressure. About 60% of participants on the highest dose moved out of the obesity BMI category, and 28.4–40% achieved normalized blood sugar depending on dose. Common side effects were gastrointestinal; seven deaths during the study were judged unrelated to treatment. Eli Lilly plans to file the data with regulators early next year.
Phase 3 Trial Puts Retatrutide at a New High-Water Mark for Weight Loss
Next-generation weight-loss medicines reached a major milestone when Eli Lilly reported phase 3 results showing that the investigational triple-receptor drug retatrutide produced average weight losses of up to 49.6 pounds (22.5 kg)—more than 20% of body weight—in people with obesity and type 2 diabetes.
The 80-week TRIUMPH-2 trial enrolled 1,152 adults with obesity and type 2 diabetes and randomized participants to receive retatrutide at 4 mg, 9 mg, or 12 mg or placebo. Average weight loss was 29.8 lb (13.5 kg) at 4 mg, 45.4 lb (20.6 kg) at 9 mg, and 49.6 lb (22.5 kg) at 12 mg; the placebo group lost 9.3 lb (4.2 kg) on average.
Clinical Benefits Beyond Weight Loss
In addition to large weight reductions, participants experienced meaningful improvements in blood glucose control and reductions in cholesterol and blood pressure—important cardiovascular risk factors. Depending on dose, between 28.4% and 40% of retatrutide recipients achieved normalized blood-glucose levels by week 80. Eli Lilly reported that roughly 60% of participants on the 12 mg dose were no longer classified as having obesity by BMI at the study’s end.
How Retatrutide Works
Retatrutide belongs to an emerging class of multi-receptor drugs often called GLP-3s. Whereas GLP-1 receptor agonists (for example, semaglutide marketed as Ozempic/Wegovy) target the GLP-1 receptor and tirzepatide targets GLP-1 and GIP, retatrutide is designed as a triple agonist that engages GLP-1, GIP and glucagon receptors. It is the first triple-agonist to report phase 3 results.
Safety, Tolerability, and Risks
Retatrutide was associated with gastrointestinal side effects in TRIUMPH-2, including diarrhea, constipation, nausea and vomiting. The Lancet report notes seven deaths occurred during the study period; investigators judged those deaths unrelated to the treatment. Independent reporting (STAT) also indicated some participants skipped doses because of side effects or concerns about the speed of weight loss.
Experts caution that rapid, substantial weight loss can increase the risk of gallstones and micronutrient deficiencies, and that careful clinical monitoring is needed if these drugs become widely used.
Broader Context and Next Steps
A separate Eli Lilly–funded trial, TRIUMPH-1, found up to a 25% average body-weight reduction over 80 weeks in people with obesity who did not have diabetes. Pharmaceutical developers are already exploring agents that target four or even five receptors as research accelerates.
“We achieved a new high-water mark for what's possible in terms of weight loss,” said Daniel Skovronsky, Chief Scientific and Product Officer at Eli Lilly.
Eli Lilly said it plans to submit the TRIUMPH-2 data to the U.S. Food and Drug Administration and other regulators early next year. If approved and widely available, clinicians and patients will need to weigh benefits, side effects, and appropriate dosing—experts expect many patients may not require the maximum dose.
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