Eli Lilly reported positive topline findings from the phase 3 TRIUMPH-1 trial evaluating retatrutide, a once-weekly, investigational, triple hormone receptor agonist that activates glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon, in adults with obesity or overweight and at least one weight-related comorbidity without diabetes. According to Eli Lilly, all retatrutide dose groups met the primary and key secondary endpoints at 80 weeks.

Participants receiving retatrutide 12 mg dose experienced a mean body weight reduction of 28.3%, averaging 70.3 pounds lost, compared with 25.9% (64.4 pounds lost) with a 9 mg dose and 19.0% (47.2 pounds lost) with a 4 mg dose. Participants assigned a placebo had a 2.2% reduction in body weight. Average baseline body weight was 248.5 pounds with a mean body mass index (BMI) of 40.

Among participants receiving retatrutide 12 mg dose, 45.3% achieved at least 30% body weight reduction at 80 weeks compared with 0.5% in the placebo group. In addition, 65.3% of participants receiving 12 mg achieved a BMI below 30 by week 80, including 37.5% of those with baseline class 3 obesity.

A prespecified extension enrolled 532 participants with baseline BMI of at least 35 who completed the initial study period without permanent dose reduction. At 104 weeks, participants continuing retatrutide 12 mg dose achieved a mean body weight reduction of 30.3%, corresponding to 85.0 pounds lost.

Retatrutide treatment was associated with reductions in waist circumference, triglycerides, systolic blood pressure, non-high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels.

The most commonly reported adverse events were gastrointestinal and included nausea, diarrhea, constipation, and vomiting. Discontinuation rates due to adverse events were 4.1% with retatrutide 4 mg dose, 6.9% with 9 mg dose, and 11.3% with 12 mg dose compared with 4.9% with placebo.

TRIUMPH-1 was a randomized, double-blind, placebo-controlled phase 3 trial that enrolled 2,339 participants. Additional findings from the TRIUMPH clinical development program are expected later this year, including studies evaluating retatrutide in obesity with type 2 diabetes and cardiovascular disease.

Source: Eli Lilly