Eli Lilly has announced positive topline results from TRIUMPH-1, a Phase III clinical trial evaluating the efficacy and safety of retatrutide, a 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, the company reported, all doses of retatrutide (4mg, 9mg and 12mg) met the primary and key secondary endpoints for obesity, delivering clinically meaningful weight loss. 

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, said: “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 the primary endpoint, participants taking retatrutide 9mg and 12mg lost an average of 64.4 lbs (25.9%) and 70.3 lbs (28.3%), respectively. Those taking the 4mg dose, with just a single dose escalation step, lost an average of 47.2 lbs (19.0%). Notably, 65.3% of participants taking retatrutide 12mg achieved a BMI <30, falling under the threshold for obesity at 80 weeks, including 37.5% of those who started with class 3 obesity (BMI ≥40). 

In a pre-specified blinded extension for those with a BMI ≥35, participants who continued on retatrutide 12mg to 104 weeks lost an average of 85.0 lbs (30.3%). 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 (hsCRP).