Eli Lilly reports retatrutide meets primary endpoint in TRIUMPH-1 study

Eli Lilly (LLY) announced topline results from TRIUMPH-1, a Phase 3 clinical trial evaluating the efficacy and safety of retatrutide, an investigational GIP, GLP-1, and glucagon triple hormone receptor agonist, in adults with obesity or overweight and at least one weight-related comorbidity and without diabetes. At 80 weeks, all doses of retatrutide met the primary and key secondary endpoints for obesity, delivering clinically meaningful weight loss. For the primary endpoint, participants taking retatrutide 9 mg and 12 mg lost an average of 64.4 lbs and 70.3 lbs, respectively. Those taking the 4 mg dose of retatrutide, with just a single dose escalation step, lost an average of 47.2 lbs. Notably, 65.3% of participants taking retatrutide 12 mg achieved a BMI less than 30, falling under the threshold for obesity at 80 weeks, including 37.5% of those who started with class 3 obesity In a pre-specified blinded extension for those with a BMI greater than or equal to 35, participants who continued on retatrutide 12 mg to 104 weeks lost an average of 85.0 lbs. Additionally, retatrutide showed significant improvements from baseline across certain cardiovascular risk factors, including waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein. For the treatment-regimen estimand, each dose level of retatrutide led to improvements across the primary and key secondary endpoints, as well as the pre-specified extension, including: percent change in body weight at 80 weeks and percent change in body weight at 104 weeks. The types of adverse events seen were generally consistent with trials of other incretin-based therapies. The most common adverse events among participants treated with retatrutide were nausea, diarrhea, constipation, vomiting and upper respiratory tract infection. Incidences of dysesthesia occurred in 5.1%, 12.3%, and 12.5% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 0.9% with placebo, and incidences of urinary tract infections occurred in 7.5%, 8.8%, and 8.4% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 5.3% with placebo. Events of dysesthesia and urinary tract infections were generally mild to moderate, the majority resolved during treatment, and most participants continued taking retatrutide. Discontinuation rates due to adverse events were 4.1%, 6.9%, 11.3%, with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 4.9% with placebo.