Global pharma powerhouse Eli Lilly and Company is reporting striking late-stage clinical trial results for its investigational obesity drug retatrutide, a first-in-class triple hormone receptor agonist targeting GIP, GLP-1, and glucagon pathways.
The company said its Phase 3 TRIUMPH-1 trial met all primary and key secondary endpoints at 80 weeks, with all tested doses—4 mg, 9 mg, and 12 mg—delivering “clinically meaningful weight loss” in adults with obesity or overweight and at least one weight-related comorbidity, and without diabetes.
“Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease,” said Ania Jastreboff, Professor of Medicine & Pediatrics (Endocrinology) at the Yale School of Medicine, Director of the Yale Obesity Research Center (Y-Weight), and lead investigator.
“It was impressive to see that every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants, and people with severe obesity on the highest dose lost on average 30% of their body weight over two years.
"Importantly, treatment with retatrutide not only resulted in robust weight reduction, but also in clear improvements in assessed cardiometabolic health measures. For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory.”
The numbers underscore the scale of the effect. Participants on 9 mg lost an average of 64.4 lbs (25.9%), while those on 12 mg shed 70.3 lbs (28.3%). Even the lowest dose, 4 mg, produced a 47.2 lb (19.0%) average weight loss.
At the highest dose, 65.3% of participants reduced their BMI below 30, moving out of the obesity range by week 80. Among those who began the study with class 3 obesity (BMI ≥40), 37.5% crossed that threshold. In a pre-specified extension, participants with BMI ≥35 who stayed on 12 mg through 104 weeks lost an average of 85.0 lbs (30.3%).
Beyond weight loss, the trial also reported broad improvements in cardiometabolic risk markers, including waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure, and high-sensitivity C-reactive protein (hsCRP).
