Retatrutide reduced body weight by up to 28.3% at 80 weeks in adults with obesity or overweight in the phase 3 TRIUMPH-1 trial.
Eli Lilly reported positive topline phase 3 results for
“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 Yale School of Medicine and lead investigator of TRIUMPH-1, said in the company announcement.1
Key Facts
TRIUMPH-1 (NCT05929066) was an 80-week, randomized, double-blind, placebo-controlled phase 3 master trial enrolling 2339 adults with obesity or overweight, without diabetes. Participants were randomized 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg, or placebo. Retatrutide was initiated at 2 mg once weekly and escalated every 4 weeks to the assigned target dose.1
For the primary endpoint using the efficacy estimand, mean body weight change at 80 weeks was −19.0% with
At 80 weeks, 45.3% of participants receiving retatrutide 12 mg achieved at least 30% body weight reduction, compared with 0.5% receiving placebo. Lilly also reported reductions in waist circumference, non–high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and high-sensitivity C-reactive protein, although full data have not yet been published in a peer-reviewed journal.1
A prespecified blinded extension included 532 participants with baseline BMI of at least 35 who completed the main trial and tolerated study medication. At 104 weeks, participants originally assigned to retatrutide 12 mg and escalated to maximum tolerated dose had mean body weight reduction of 30.3%, or 38.5 kg, from an extension baseline mean weight of 121.7 kg. This extension population was enriched for completers and tolerators, limiting interpretation relative to the full randomized cohort.1
Safety findings were generally consistent with incretin-based obesity pharmacotherapy, with gastrointestinal adverse events most common. Nausea occurred in 28.6%, 38.4%, and 42.4% of participants receiving retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared to 14.8% with placebo. Vomiting occurred in 10.6%, 22.8%, and 25.3% compared to 4.8%. Dysesthesia was reported more often with retatrutide than placebo, reaching 12.5% in the 12-mg group compared to 0.9% with placebo. Discontinuation due to adverse events was 4.1%, 6.9%, and 11.3% across retatrutide doses compared to 4.9% with placebo.1
The findings extend earlier phase 2 data, in which retatrutide produced dose-dependent weight reduction through 48 weeks in adults with obesity.2 They also enter a treatment landscape reshaped by incretin therapies, including tirzepatide, which produced mean weight reductions up to 20.9% at 72 weeks in SURMOUNT-1 and is approved for chronic weight management in adults with obesity or overweight and weight-related comorbidity.3,4
For clinicians, the main question is not whether retatrutide can produce substantial weight loss in selected trial participants, but how its efficacy, tolerability, durability, cardiometabolic effects, and safety compare with available therapies in broader practice. Lilly said additional TRIUMPH-1 data will be presented at the American Diabetes Association Scientific Sessions, with TRIUMPH-2 in adults with type 2 diabetes and TRIUMPH-3 in established cardiovascular disease expected later.1
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