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News|Articles|July 23, 2026
Retatrutide Delivers Up to 22.6% Weight Loss in Two New Phase III Trials
Author(s)Nicholas Jacobus
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Key Takeaways
- TRIUMPH-2 (n=1,152) met its primary endpoint, showing 12.7%–20.8% mean weight loss across 4–12 mg versus 4.0% with placebo at 80 weeks.
- Glycemic efficacy in TRIUMPH-2 included A1C reductions up to 1.6 percentage points from a 7.7% baseline versus 0.2 percentage points with placebo.
- Gastrointestinal adverse events predominated, with AE-related discontinuations of 3.8%–11.6% on retatrutide versus 4.9% on placebo.
- TRIUMPH-3 (n=1,949) demonstrated 21.6%–22.6% mean weight loss with 9–12 mg versus 3.2% with placebo, plus substantial improvements in lipids, BP, hsCRP, and waist circumference.
- MACE-5 HR was 0.82 (95% CI, 0.55–1.22) and MACE-3 HR was 1.12 (95% CI, 0.64–1.96), reflecting low event rates and no statistical significance.
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Eli Lilly’s Retatrutide met primary endpoints in two Phase III trials, delivering up to 22.6% body weight loss in adults with severe obesity and cardiovascular disease
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Eli Lilly and Company reported positive topline results from the Triumph-2 and Triumph-3 pivotal Phase III trials evaluating Retatrutide
The treatment, an investigational once-weekly triple hormone receptor agonist targeting GIP, GLP-1, and glucagon receptors simultaneously, met its primary endpoints in both trials, delivering substantial weight loss across high-risk populations including adults with type 2 diabetes and those with severe obesity and established cardiovascular disease.1The results bring the total number of positive Phase III studies for Retatrutide to five, with Lilly saying it plans to submit a biologics license application for U.S. approval in the first quarter of 2027.
What did Triumph-2 show?
Triumph-2 enrolled 1,152 adults with type 2 diabetes and obesity or overweight, randomized to Retatrutide 4 mg, 9 mg, 12 mg, or placebo over 80 weeks.2 All three doses met the primary endpoint, with participants loosing an average of 29.8 lbs (12.7%) on the 4 mg dose, 45.4 lbs (19.1%) on the 9 mg dose, and 49.6 lbs (20.8%) on the 12 mg dose, compared to 9.3 lbs (4.0%) on placebo.2 Glycemic control also improved, with A1C reductions of up to an average of 1.6 percentage points across the active arms versus 0.2 percentage points for placebo, from a baseline A1C of 7.7%.
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The most common adverse events were gastrointestinal in nature and include, diarrhea, nausea, constipation, decreased appetite, and vomiting, with most resolving during treatment.2Discontinuation rates due to adverse events ranged from 3.8% to 11.6% across the Retatrutide doses, compared to 4.9% for placebo
What did Triumph-3 show?
Triumph-3 enrolled 1,949 adults with severe obesity, defined as BMI of 35 kg/m² or higher, and established cardiovascular disease, with or without type 2 diabetes.3 At 80 weeks, participants on the 9 mg dose lost an average of 52.7 lbs (21.6%) and those on the 12 mg dose lost an average of 55.8 lbs (22.6%), compared to 7.7 lbs (3.2%) for placebo.3
Beyond weight loss, the highest dose delivered meaningful reductions in cardiovascular risk factors: triglycerides fell by an average of 37.0%, non-HDL cholesterol by 16.5%, systolic blood pressure by 9.3 mmHg, waist circumference by 7.5 inches and high-sensitivity C-reactive protein by 51.2%
Triumph-3 also examined major adverse cardiovascular events, though the data are nuanced. Major adverse cardiovascular events occurred less frequently than anticipated in both the Retatrutide and placebo arms.3 In a pre-specified analysis of time to first MACE-5, a composite of all-cause death, heart attack, stroke, heart failure event or coronary revascularization, there were 44 events in the Retatrutide group versus 52 in the placebo group, yielding a hazard ratio of 0.82 (95% CI: 0.55 to 1.22).1 For the narrower MACE-3 composite of cardiovascular death, heart attack or stroke, there were 27 events in the Retatrutide arm and 23 in the placebo arm, for a hazard ratio of 1.12 (95% CI: 0.64 to 1.96).
Neither result crossed the threshold for statistical significance, and the wide confidence intervals reflect the lower-than-expected event rates
What comes next?
“Across five positive Phase III studies, Retatrutide has shown powerful efficacy, and we believe it could be an important future tool in the management of cardiometabolic health,” said Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health. “We now have the clinical data package to support global submissions for Retatrutide as a potential treatment for obesity, knee osteoarthritis pain, and obstructive sleep apnea.”
Lilly says it is completing the chemistry, manufacturing and controls data package required for a biologics license application and plans to submit it to FDA by Q1 2027.1Detailed results from both trials will be presented at future medical meetings and published in peer-reviewed journals
Sources
- Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C Eli Lilly and CompanyJuly 23, 2026 https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional
- A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight (TRIUMPH-2) National Library of MedicineApril 13, 2026 https://clinicaltrials.gov/study/NCT05929079
- A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease (TRIUMPH-3) National Library of MedicineMay 22, 2026, https://clinicaltrials.gov/study/NCT05882045
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