EASD 2026: Retatrutide nears 19% weight loss in obesity with type 2 diabetes

Clinical takeaway: In adults with obesity or overweight and type 2 diabetes, once-weekly retatrutide (not yet approved in the US) produced substantial weight loss and improved glycemic control through 80 weeks, with nearly half of patients on the highest dose losing at least 20% of their body weight. GI adverse events were common and treatment discontinuations increased at higher doses.

Weight loss is typically more difficult to achieve in people with obesity who also have type 2 diabetes than in those without diabetes. Retatrutide, an investigational triple agonist targeting glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors, is being studied as a potential next-generation obesity treatment. These findings were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2026 and published in The Lancet.

In the phase 3 TRIUMPH-2 trial, 1,152 adults with obesity or overweight and type 2 diabetes were randomized to placebo or once-weekly retatrutide 4 mg, 9 mg, or 12 mg for 80 weeks. Participants had a mean BMI of 38 kg/m² and a mean HbA1c of 7.7%, and more than 90% were taking oral glucose-lowering therapy at baseline.

Mean weight loss at week 80 reached 11.9%, 16.8%, and 18.8% with retatrutide 4 mg, 9 mg, and 12 mg, respectively, versus 5.1% with placebo. At the 12-mg dose, 47% of participants lost at least 20% of their starting weight and 31% lost at least 25%, compared with 6% and 3% of placebo recipients. HbA1c fell by roughly 1.4%-1.5% with retatrutide versus 0.45% with placebo, and 72% of participants receiving 12 mg achieved an HbA1c of 6.5% or lower, compared with 29% in the placebo group.

Retatrutide was also associated with improvements in waist circumference, systolic blood pressure, triglycerides, non-HDL cholesterol, inflammatory markers, and quality-of-life measures. The most common adverse events were gastrointestinal, including diarrhea (27%-34%) and nausea (14%-28%). Treatment discontinuation due to adverse events occurred in 12% of patients receiving 9 mg and 8% receiving 12 mg, compared with 5% receiving placebo. Investigators reported that all 7 deaths observed during the study were unrelated to treatment.

“Findings from TRIUMPH-2 suggest that retatrutide may advance the treatment of obesity and type 2 diabetes, a population in which weight reduction has been challenging to achieve,” the authors said.

Source: Bellido V, et al. (2026 Sep 29) The Lancet. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomized, placebo-controlled, phase 3 trial