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In the phase III TRIUMPH-2 trial, adults with obesity and type 2 diabetes lost an average of 11.9% to 18.8% of body weight after 80 weeks on retatrutide, depending on dose; the placebo group lost 5.1%. The investigational drug also reduced HbA1c, but it is not approved, and the trial did not compare it directly with other weight-loss medicines.
Retatrutide produced average weight loss of 11.9% to 18.8% after 80 weeks in adults with obesity and type 2 diabetes in the phase III TRIUMPH-2 trial, compared with 5.1% with placebo, according to results presented at the European Association for the Study of Diabetes (EASD) annual meeting and published in The Lancet. The investigational drug also improved blood sugar measures, but it is not approved and its safety and effectiveness have not been compared directly with other active weight-loss medicines in this trial.
The double-blind trial enrolled 1,152 adults at 92 medical and research centers in eight countries. Participants had a body mass index of at least 27, type 2 diabetes, and a history of attempts to lose weight through diet. They were randomly assigned to once-weekly injections of retatrutide at 4 mg, 9 mg or 12 mg, or placebo, alongside stable background glucose-lowering treatment.
At week 80, average weight loss in the treatment-regimen analysis was 11.9% (28.4 pounds) with 4 mg, 16.8% (40.3 pounds) with 9 mg and 18.8% (45.6 pounds) with 12 mg. The placebo group lost 5.1% (12.8 pounds). In a separate efficacy analysis, which assumes participants followed the treatment as intended and excludes certain events that could affect results, weight loss reached 20.8% at the highest dose. That estimate uses a different analysis method from the treatment-regimen figures.
Average HbA1c, a measure of blood sugar over time, fell by 1.38 to 1.50 percentage points across the retatrutide doses, compared with a 0.45-point decline with placebo. The study reported that up to 40% of participants receiving retatrutide reached normoglycemia, defined as HbA1c below 5.7%. Some cardiometabolic measures, including waist circumference, triglycerides, non-HDL cholesterol and high-sensitivity C-reactive protein, also declined. The reported percentages for those measures are changes from baseline, not comparisons with placebo.
Weight Loss in Type 2 Diabetes
The results address a treatment challenge highlighted by the researchers: people with type 2 diabetes tend to lose less weight than people without diabetes, including with medication or metabolic surgery. The TRIUMPH-2 findings suggest retatrutide may produce substantial weight reduction in this group while also improving blood sugar measures. That combination matters to patients and clinicians weighing options for obesity and diabetes, but the trial results do not establish how retatrutide compares with currently available medicines or what its longer-term effects may be.
Juan P. Frias, the study presenter from the Los Angeles Institute for Metabolic Research, said the weight loss in this trial reached a level previously seen with anti-obesity drugs mainly in patients without diabetes. He also cautioned, in discussing the efficacy analysis, that its result remained below the 28.3% weight loss reported in TRIUMPH-1, a trial in people without diabetes. Those figures come from different trials and populations, so they are not a direct head-to-head comparison.
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How TRIUMPH-2 Fits the Evidence
Retatrutide is an investigational medicine that activates three hormone receptors: GIP, GLP-1 and glucagon. Frias told the EASD meeting that engaging these pathways may help explain the weight loss seen in the study. The trial did not test that explanation directly, and its findings do not establish which mechanism contributed most.
Previous clinical trial data cited in the report found average weight losses of 13.2% with high-dose semaglutide and 15.7% with tirzepatide in people with diabetes. Those results provide context, but because the medicines were not compared within TRIUMPH-2, they cannot show that retatrutide is more effective. The report also described separate EASD data for eloralintide combined with tirzepatide; those findings are from another investigational treatment and a separate study.
“We know that people with type 2 diabetes lose less weight than people without diabetes. We see this irrespective of the weight-loss method, whether it’s pharmacotherapy or metabolic surgery.”
— Juan P. Frias, MD, presenting the findings at the EASD annual meeting
Safety and Comparisons Still Open
Gastrointestinal events, mainly nausea, diarrhea and constipation, were the most common adverse events. Discontinuation because of gastrointestinal symptoms was reported in 0% to 2% of retatrutide groups and 1% of the placebo group. Overall, 3% to 11% of participants in retatrutide groups stopped study treatment because of adverse events, compared with 5% receiving placebo. Hypotension and dysesthesia occurred more often in retatrutide groups.
Seven participants died during the trial; the report says investigators judged all deaths unrelated to the study interventions. The study did not include an active comparator, and it did not measure body composition to determine how much weight loss came from fat versus lean mass. The supplied results do not establish long-term outcomes beyond the study period or how the drug would perform in people outside the trial’s eligibility criteria.
FDA Submission Planned for 2027
Eli Lilly, which is developing retatrutide, said it plans to submit the data to the U.S. Food and Drug Administration for an approval application in early 2027. That is a planned milestone, not an approval decision; the drug remains investigational. The results and any additional evidence submitted to regulators will inform whether it is authorized and what its approved use, if any, would be.
Until regulatory review is complete, patients should not treat retatrutide as an available prescription option. The report notes that social media attention has contributed to a gray market for the unapproved drug, but it does not provide evidence about the quality or safety of products sold through those channels.
Key Questions
How much weight did participants lose with retatrutide?
At week 80, average weight loss in the treatment-regimen analysis ranged from 11.9% with 4 mg to 18.8% with 12 mg. Participants receiving placebo lost an average of 5.1%. A separate efficacy analysis reported 20.8% average weight loss at the highest dose and should not be confused with the treatment-regimen result.
Did retatrutide improve blood sugar measures?
Yes. Average HbA1c fell by 1.38 to 1.50 percentage points in the retatrutide groups, compared with a 0.45-point decline with placebo. Up to 40% of retatrutide-treated participants reached the study’s definition of normoglycemia, an HbA1c below 5.7%.
Is retatrutide approved for use?
No. Retatrutide is investigational. Eli Lilly said it plans to submit data to the FDA in early 2027; a planned submission does not mean the drug has been approved.
Was retatrutide compared directly with semaglutide or tirzepatide?
No. TRIUMPH-2 compared retatrutide doses with placebo, not with another active medicine. Weight-loss figures from separate trials can provide background, but they do not establish which drug works better.
What side effects were reported?
The most frequent adverse events were nausea, diarrhea and constipation. Overall treatment discontinuation because of adverse events ranged from 3% to 11% across retatrutide groups, compared with 5% on placebo; hypotension and dysesthesia were reported more often with retatrutide.
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