TRIUMPH-1: Retatrutide Substantially Lowers Weight, BMI in Patients With Obesity or Overweight

Retatrutide, Eli Lilly’s GLP-1/GIP/glucagon triple agonist, has substantially reduced body weight among patients with obesity in the TRIUMPH-1 trial, moving them below the clinical threshold for obesity.1

Presented at the American Diabetes Association (ADA) Scientific Sessions 2026 in New Orleans, Louisiana, by Ania Jastreboff, MD, PhD, the Harvey and Kate Cushing Professor of Medicine and professor of pediatrics at Yale School of Medicine, these data highlight retatrutide’s substantial efficacy in patients with overweight or obesity, alongside similarly positive results from the TRANSCEND-T2D-1 trial.1

“In TRIUMPH-1 and TRANSCEND-T2D-1, treatment with retatrutide resulted in substantial weight reduction together with clinically meaningful improvements in glycemia, knee osteoarthritis pain, and obstructive sleep apnea, with many individuals reaching what are classified as healthy-range weight and normal blood sugar levels,” Ania Jastreboff, MD, PhD, professor of medicine and pediatrics at the Yale School of Medicine, director of the Yale Obesity research Center, and lead investigator of TRIUMPH-1. “These findings demonstrate what may be possible when we treat obesity and impact overall health, and what this could mean for people living with obesity and its related complications.”1

TRIUMPH-1 is a phase 3, randomized, double-blind, placebo-controlled master trial comparing retatrutide’s safety and efficacy versus placebo in adults with overweight and obesity. In addition, the study included 2 basket trials for knee osteoarthritis pain and moderate-to-severe obstructive sleep apnea. The trial ran for 80 weeks, with 2339 patients randomly assigned in a 1:1:1:1 ratio to either retatrutide 4 mg, 9 mg, 12 mg, or placebo. Those assigned to retatrutide began treatment with 2 mg once weekly before increasing in a stepwise approach every 4 weeks to the target dose.1

Patients were eligible for inclusion if they had a body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 with hypertension, dyslipidemia, obstructive sleep apnea, and/or cardiovascular disease. Patients were excluded if they had a self-reported or documented change in body weight >11 lbs within 90 days, had taken weight loss drugs within 90 days, had a prior or planned surgical treatment for obesity, or had diabetes mellitus or pancreatitis, among other criteria.2

The study’s primary endpoint was the percent change from baseline in body weight at week 80. Key secondary endpoints included change in BMI, waist circumference, systolic blood pressure, fasting insulin, and HbA1c, among others. Retatrutide met this primary endpoint by week 80, with patients on retatrutide 9 and 12 mg losing an average of 64.4 lbs (25.9%) and 70.3 lbs (28.3%), respectively. Patients receiving the 4 mg dose lost an average of 47.2 lbs (19%).1

Additionally, 65.3% of participants on retatrutide 12 mg achieved a BMI <30, and 33.3% achieved a BMI <25. These values are below the minimum threshold for a clinical diagnosis of obesity. In a prespecified extension for patients with a baseline BMI ≥35, those receiving the 12 mg dose lost an average of 85 lbs (30.3%).1

The basket trials also demonstrated positive results, with retatrutide reducing Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores by ≤4.3 points (73.1%) from a baseline of 6 among patients with knee osteoarthritis and apnea-hypopnea index (AHI) by ≤36.1 events per hour (60.6%) from a baseline of 58.6 events per hour in patients with obstructive sleep apnea.1

The most common adverse events in TRIUMPH-1 in retatrutide 4 mg, 9 mg, 12 mg, and placebo, respectively, were nausea (28.8%, 38.4%, 42.4% vs 14.8%), diarrhea (25.2%, 34.1%, 32% vs 13.5%), constipation (23.8%, 25.9%, 26.1% vs 10.9%), vomiting (10.6%, 22.8%, 25.3% vs 4.8%), and upper respiratory tract infection (14.2%, 12.2%, 13.1% vs 11.6%). Dysesthesia (5.1%, 12.3%, 12.5% vs 0.9%) and urinary tract infections (7.5%, 8.8%, 8.4% vs 5.3%) were also noted, although these were generally mild to moderate and most resolved during treatment.1

“This is why it’s important to conduct these trials across multiple diseases with these molecules,” Jastreboff said in a press briefing at ADA 2026. “Think about the direct disease-modifying effects of these medicines - they can impact weight loss, but they can also affect progression of disease, or how a disease evolves in a person over their lifetime. We have to look at the different mechanisms of each molecule individually as well.”

References

1. Jastreboff A, et al. Results of First Phase 3 Study of Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist in Patients with Obesity (TRIUMPH-1). Abstract presented at the American Diabetes Association (ADA) Scientific Sessions 2026, New Orleans, LA. June 5-8, 2026.

2. Eli Lilly and Company. A Study of Retatrutide (LY34437943) in Participants Who Have Obesity or Overweight (TRIUMPH-1). ClinicalTrials.gov Identifier: NCT05929066. Updated June 3, 2026. Accessed June 6, 2026. https://clinicaltrials.gov/study/NCT05929066

3. Eli Lilly. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026. Accessed June 6, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss