Retatrutide Meets Weight Loss Endpoints in Phase 3 Obesity Trial

Eli Lilly has reported topline phase 3 results for retatrutide in adults with obesity or overweight and ≥1 weight-related comorbidity, with all tested doses meeting the primary and key secondary endpoints for weight reduction at 80 weeks, according to a May 21, 2026 announcement.1

“TRIUMPH-1 highlights the importance of options and the potential for retatrutide to help people across various stages of their obesity journey,” Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, said in a statement. “From the 4 mg dose, reaching nearly 20% weight loss with 1 escalation step, to the 12 mg dose that delivered a level of weight loss associated with bariatric surgery, retatrutide offers the potential for a patient-centric approach to obesity.”1

The company-reported data come from TRIUMPH-1, a randomized, double-blind, placebo-controlled phase 3 trial evaluating once-weekly retatrutide, a triple agonist targeting glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors. The reported analysis included adults without diabetes, a clinically relevant distinction given ongoing development programs for obesity both with and without type 2 diabetes (T2D).1,2

TRIUMPH-1 Results

TRIUMPH-1 randomized 2339 participants in a 1:1:1:1 ratio to retatrutide 4 mg, 9 mg, 12 mg, or placebo. Participants initiated retatrutide at 2 mg once weekly and escalated every 4 weeks to target doses. The mean baseline body weight was 112.7 kg (248.5 lb), with a mean BMI of 40.0 kg/m2.1,2

For the efficacy endpoint at 80 weeks, mean body weight reduction was 19.0% with retatrutide 4 mg, 25.9% with 9 mg, and 28.3% with 12 mg, compared with 2.2% with placebo. In absolute terms, the corresponding reductions were 21.4 kg, 29.2 kg, and 31.9 kg vs 2.5 kg with placebo.1

Several categorical weight-loss thresholds also favored retatrutide. At 80 weeks, 62.5% of participants receiving 12 mg achieved ≥25% weight loss, 45.3% achieved ≥30% weight loss, and 27.2% achieved ≥35% weight loss. In the placebo group, those proportions were 2.2%, 0.5%, and 0.3%, respectively. Investigators also reported reductions in waist circumference and improvements from baseline in selected cardiometabolic measures, including non-HDL cholesterol, triglycerides, systolic blood pressure, and high-sensitivity C-reactive protein.1

A pre-specified blinded extension enrolled 532 participants with baseline BMI ≥35 kg/m2 who completed the 80-week study and tolerated assigned treatment. At 104 weeks, participants initially assigned to retatrutide 12 mg and escalated to maximum tolerated dose had a mean weight loss of 30.3%, or 38.5 kg.1

Safety Findings Reported With Retatrutide

Adverse events reported with retatrutide were generally consistent with other incretin-based therapies. The most common events were gastrointestinal. Nausea occurred in 28.6%, 38.4%, and 42.4% of participants assigned to retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 14.8% with placebo. Diarrhea occurred in 25.2%, 34.1%, and 32.0% vs 13.5%; constipation in 23.8%, 25.9%, and 26.1% vs 10.9%; and vomiting in 10.6%, 22.8%, and 25.3% vs 4.8%.1

The company also reported dysesthesia in 5.1%, 12.3%, and 12.5% of participants receiving retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 0.9% receiving placebo. Urinary tract infection occurred in 7.5%, 8.8%, and 8.4% of retatrutide-treated participants vs 5.3% with placebo. Most of these events were characterized as mild to moderate, and most participants continued treatment. Discontinuation due to adverse events occurred in 4.1% of participants receiving retatrutide 4 mg, 6.9% receiving 9 mg, and 11.3% receiving 12 mg, compared with 4.9% receiving placebo.1

Retatrutide Mechanism, Development, and Next Steps

Retatrutide is designed as a once-weekly agonist of GIP, GLP-1, and glucagon receptors. Earlier phase 2 data published in 2023 supported additional study of the molecule in obesity.3

The broader TRIUMPH program is evaluating retatrutide across multiple obesity-related settings, including obesity or overweight with T2D, established cardiovascular disease, knee osteoarthritis pain, moderate to severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease. The company stated additional TRIUMPH-1 results will be presented at the 86th annual American Diabetes Association Scientific Sessions, with more detailed results expected at future medical meetings and in peer-reviewed publications.1,2

Lilly also indicated results from TRIUMPH-2, evaluating retatrutide in adults with obesity or overweight and T2D, and TRIUMPH-3, evaluating adults with obesity or overweight and established cardiovascular disease, are expected later this year. Until regulatory review is complete, retatrutide remains legally available only to clinical trial participants.1

“Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease,” 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, said in a statement. “For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory.”1

References

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

2. Eli Lilly and Company. A Study of Retatrutide (LY3437943) in Participants Who Have Obesity and Overweight (TRIUMPH-1). ClinicalTrials.gov Identifier: NCT05929066. Updated April 18, 2025. Accessed May 21, 2026. https://clinicaltrials.gov/study/NCT05929066

3. Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972