Eli Lilly has reported positive topline results from two additional Phase 3 studies in its TRIUMPH clinical development programme, further establishing the efficacy of retatrutide, an investigational first-in-class triple hormone receptor agonist targeting glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors. The TRIUMPH-2 and TRIUMPH-3 trials evaluated retatrutide in adults with obesity complicated by type 2 diabetes and established cardiovascular disease, respectively. Both studies successfully met their primary efficacy endpoints after 80 weeks of treatment
In TRIUMPH-2, adults with obesity or overweight and type 2 diabetes achieved substantial dose-dependent weight loss. Participants receiving the highest evaluated dose (12 mg) experienced a mean body weight reduction of 20.8% (49.6 lb or 22.5 kg), compared with 4.0% in the placebo group. Clinically meaningful improvements in glycaemic control were also observed, with HbA1c reductions reaching up to 1.6% from a baseline of 7.7%, highlighting retatrutide’s dual benefits in weight management and diabetes control.
TRIUMPH-3 enrolled adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes. At 80 weeks, participants receiving retatrutide achieved mean weight reductions of up to 22.6% (55.8 lb or 25.3 kg), substantially exceeding placebo. In addition to weight loss, retatrutide produced favourable effects on multiple cardiometabolic risk factors, including reductions in triglycerides, non-HDL cholesterol, systolic blood pressure, waist circumference, and high-sensitivity C-reactive protein (hsCRP). While exploratory analyses of major adverse cardiovascular events (MACE) were not powered to demonstrate cardiovascular benefit, event rates remained low, and no definitive cardiovascular safety concerns emerged. Gastrointestinal adverse events, including nausea, diarrhoea, and vomiting, were the most frequently reported treatment-related events and were generally consistent with the incretin drug class.
Together with previously reported positive Phase 3 studies, these findings demonstrate consistent efficacy across diverse obesity populations, including those with complex metabolic and cardiovascular comorbidities. Lilly has announced that the accumulated Phase 3 evidence will support a Biologics License Application (BLA) submission to the US FDA in the first quarter of 2027, positioning retatrutide as a promising next-generation therapy for obesity and its associated complications.
