Eli Lilly's investigational triple hormone agonist retatrutide demonstrates substantial weight loss and glycemic control improvements in adults with type 2 diabetes and obesity. Results from the phase III TRIUMPH-2 trial, presented at the EASD 2026 meeting and published in The Lancet, show that patients on the highest 12-mg dose achieved an average weight loss of up to 20.8% and 72% reached target HbA1c levels of 6.5% or lower. Gastrointestinal side effects like nausea and diarrhea were common.
Weight loss Outcomes in TRIUMPH-2
- ▪At the maximum 12-mg dose of retatrutide in the TRIUMPH-2 trial, 47% of participants lost at least 20% of their starting weight, and 31% lost a quarter or more of their body weight.
- ▪In the TRIUMPH-2 treatment regimen estimand, participants taking retatrutide achieved average body weight losses of 11.9% with the 4-mg dose, 16.8% with the 9-mg dose, and 18.8% with the 12-mg dose at week 80.
- ▪In the TRIUMPH-2 efficacy estimand, which assumes participants take the medication as intended, retatrutide produced average body weight losses of 19.1% for the 9-mg dose and 20.8% for the 12-mg dose at week 80.
Glycated hemoglobin reductions in TRIUMPH-2
- ▪In the TRIUMPH-2 trial, retatrutide treatment atop background diabetes therapy resulted in mean HbA1c reductions of 1.38% with the 4-mg dose, 1.50% with the 9-mg dose, and 1.45% with the 12-mg dose.
- ▪In the TRIUMPH-2 trial, 72% of participants receiving retatrutide achieved a glycated hemoglobin HbA1c reading of 6.5% or lower at week 80, compared to 29% of participants receiving the placebo.
Adverse events and safety in TRIUMPH-2
- ▪In the TRIUMPH-2 trial, hypotension occurred in 1% to 6% of participants receiving retatrutide, compared to less than 1% of those receiving the placebo.
- ▪The most frequent adverse events reported during the TRIUMPH-2 trial were gastrointestinal, with diarrhea occurring in 27% to 34% of retatrutide-treated participants and nausea occurring in 14% to 28% of retatrutide-treated participants.
- ▪Permanent treatment discontinuation due to adverse events in the TRIUMPH-2 trial occurred in 12% of participants in the 9-mg retatrutide group and 8% of participants in the 12-mg retatrutide group.
- ▪Seven deaths occurred during the TRIUMPH-2 trial, but clinical investigators determined that all seven deaths were unrelated to the retatrutide study intervention.
TRIUMPH-2 trial design and participants
- ▪In the TRIUMPH-2 trial, 1,152 participants were randomized to receive once-weekly subcutaneous injections of either a placebo or retatrutide in doses of 4 mg, 9 mg, or 12 mg.
- ▪The phase III TRIUMPH-2 clinical trial of Eli Lilly's investigational drug retatrutide was conducted across 92 sites in eight countries and enrolled 1,152 adults with type 2 diabetes and obesity or overweight.
- ▪The TRIUMPH-2 trial enrolled participants with a body mass index of at least 27, a mean baseline glycated hemoglobin HbA1c of 7.71%, and a history of at least one unsuccessful dietary weight-loss attempt.
Debatable claims
- ▪Engaging three hormonal pathways is necessary for effective weight loss in type 2 diabetes
- ▪Retatrutide's weight-loss benefits outweigh its adverse side effects
- ▪Obesity treatment should be the primary strategy for managing type 2 diabetes
- ▪Prescribing retatrutide is premature without long-term body composition data
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