Eli Lilly’s latest weight-loss candidate is poised to disrupt the obesity drug market and could give current market leaders a run for their money.
The Indiana-based pharmaceutical company recently announced positive results from its pivotal TRIUMPH-1 Phase 3 trial, showing that retatrutide, an investigational once-weekly triple hormone receptor agonist, delivered substantial and clinically meaningful weight reduction in adults living with obesity or overweight.
According to Lilly, retatrutide activates the body’s receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon.
The TRIUMPH-1 enrolled adults with obesity or overweight and at least one weight-related comorbidity, excluding individuals with diabetes. At 80 weeks, all tested doses of retatrutide (4 mg, 9 mg, and 12 mg) achieved the study’s primary and key secondary endpoints for obesity, delivering clinically meaningful weight loss
Participants taking retatrutide 9 mg lost an average of 64.4 lbs (25.9%) while those on 12 mg lost 70.3 lbs (28.3%). Those taking the 4 mg dose lost an average of 47.2 lbs (19.0%).Notably, more than 65% of participants receiving the 12 mg dose achieved a BMI <30, falling under the threshold for obesity at 80 weeks, including 37.5 per cent of those who started with class 3 obesity (BMI ≥40).
In an extension study involving participants with a BMI ≥35, individuals who continued receiving retatrutide 12 mg for 104 weeks lost an average of 85.0 lbs (30.3%). Additionally, retatrutide demonstrated 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).
“Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease,” said lead investigator Ania Jastreboff, Professor of Medicine & Pediatrics (Endocrinology) at the Yale School of Medicine, Director of the Yale Obesity Research Center (Y-Weight).
“For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory,” she added.
Lilly sees retatrutide as part of a broader portfolio approach to obesity care alongside its existing therapies Zepbound (tirzepatide) and Foundayo (orforglipron).
“From the 4 mg dose, reaching nearly 20% weight loss with one escalation step, to the 12 mg dose that delivered a level of weight loss long associated with bariatric surgery, retatrutide offers the potential for a patient-centric approach to obesity. Together with Zepbound and Foundayo, retatrutide could build on Lilly’s commitment to match treatments to the needs and preferences of patients,” said Kenneth Custer, executive vice president and president, Lilly Cardiometabolic Health.
The company plans to release additional data from the TRIUMPH Phase 3 clinical trial program later this year, including results from TRIUMPH-2, which is evaluating retatrutide in adults with obesity or overweight and type 2 diabetes, and TRIUMPH-3, which is evaluating retatrutide in adults with obesity or overweight and established cardiovascular disease.
