--- title: Retatrutide, Lilly's Triple Agonist Obesity Drug, Posts Up to 22.6% Weight Loss in Phase 3 Trials description: "Lilly reports retatrutide Phase 3 results: up to 55.8 lbs lost over 80 weeks. Here is how the triple agonist compares to approved GLP-1 drugs." author: Darie Nani (Editor-in-Chief) updated: 2026-07-25T09:19:55.952Z canonical: https://www.sovereignmagazine.com/article/retatrutide-lilly-s-triple-agonist-obesity-drug-posts-up-to-22-6-weight-loss-in-phase-3-trials categories: Science & Tech content_type: News region: Global publication: Sovereign Magazine schema_type: Article --- Retatrutide, Eli Lilly's experimental triple hormone agonist, produced an average weight loss of up to 55.8 pounds, or 22.6% of body weight, over 80 weeks in adults with severe obesity and established cardiovascular disease, the company said on July 23, 2026. The result came from TRIUMPH-3, one of two Phase 3 trials that met their primary endpoint; the other, TRIUMPH-2, tested adults who also have type 2 diabetes and found smaller losses of up to 49.6 pounds, or 20.8%, over the same period. The gap between the two trials matters. Diabetes tends to blunt weight loss on GLP-1 class drugs, and Lilly's own trial design reflects that: TRIUMPH-2 enrolled a group the company has called harder to treat, and its top result still lagged TRIUMPH-3's by nearly two percentage points. Retatrutide is not approved anywhere and is not available to patients. Lilly said it plans to submit a Biologics License Application to the Food and Drug Administration in the first quarter of 2027, a filing that has not yet happened and does not guarantee approval. ## What Is a Triple Agonist Weight Loss Drug Retatrutide activates three hormone receptors in one molecule: GIP, GLP-1 and glucagon. Lilly's approved drug Zepbound (tirzepatide) activates two of those, GIP and GLP-1. Novo Nordisk's Wegovy (semaglutide) activates one, GLP-1 alone. The added glucagon target is meant to increase energy expenditure alongside appetite suppression, which is the mechanism Lilly points to when it calls retatrutide first in class. The company is also studying the drug for knee osteoarthritis pain and obstructive sleep apnea, though those trials are separate from TRIUMPH-2 and TRIUMPH-3. ## How Retatrutide's Trial Results Compare to Approved GLP-1 Drugs TRIUMPH-2 and TRIUMPH-3 were placebo-controlled trials, not head-to-head studies against Zepbound or Wegovy, so Lilly's results cannot be read as a direct win over either drug. The comparison that can be made is against each drug's own placebo-controlled data. Novo Nordisk reports that patients on its Wegovy pen lost an average of 19% of body weight, about 47 pounds, over 72 weeks in a trial that excluded people with type 2 diabetes, against 4% for placebo. Retatrutide's 22.6% figure in TRIUMPH-3 came from a longer, 80-week trial in a different population: people with severe obesity and existing heart disease. Lilly has not published a specific efficacy percentage for tirzepatide's own pivotal trials that would allow a clean side-by-side figure, so any comparison should be read as a rough sense of where the drugs sit rather than a settled ranking. ## What the Cardiovascular Data Shows TRIUMPH-3 also tracked major adverse cardiovascular events, a secondary measure. Lilly recorded 44 such events among patients on retatrutide against 52 on placebo, a hazard ratio of 0.82. The confidence interval on that figure, 0.55 to 1.22, crosses 1.0, which means the result is not statistically significant and cannot be described as retatrutide reducing cardiovascular risk. What the trial did find, at the highest dose, were measured reductions in several risk factors: triglycerides fell 37.0%, non-HDL cholesterol fell 16.5%, systolic blood pressure fell 9.3 mmHg, waist circumference fell 7.5 inches and a marker of inflammation, hsCRP, fell 51.2%. Side effects were mostly gastrointestinal. Diarrhea, nausea and constipation were the most common, and discontinuation due to adverse events ran as high as 13.5% at the top TRIUMPH-3 dose, against 4.8% on placebo. > "Across five positive Phase 3 studies, retatrutide has shown powerful efficacy, and we believe it could be an important future tool in the management of cardiometabolic health." > — Kenneth Custer, Executive Vice President and President, Lilly Cardiometabolic Health ## What Happens Next Before Retatrutide Reaches Patients Custer said the results give Lilly the data package it needs to pursue global filings for obesity, knee osteoarthritis pain and obstructive sleep apnea. The company still has to finish the chemistry, manufacturing and controls package required for a Biologics License Application before it can file, a step it expects to complete ahead of a planned Q1 2027 submission to the FDA. Full trial data have not yet been published in a peer-reviewed journal; Lilly said detailed results will be presented at future medical meetings. ## FAQ **Q: What are the results of the Phase 3 retatrutide clinical trials?** In TRIUMPH-2, adults with obesity or overweight and type 2 diabetes lost up to an average of 49.6 pounds, or 20.8% of body weight, over 80 weeks. In TRIUMPH-3, adults with severe obesity and established cardiovascular disease lost up to an average of 55.8 pounds, or 22.6%, over the same period. Both trials were placebo-controlled and met their primary endpoints. **Q: Do you lose more weight with tirzepatide (Zepbound) or retatrutide?** There is no head-to-head trial comparing the two drugs, and Lilly has not published a specific efficacy percentage from tirzepatide's own pivotal trials, so a direct comparison cannot be made from public data. Retatrutide adds a third hormone target, glucagon, to the two that tirzepatide activates, which is the mechanism Lilly cites for its results, but that difference in design has not been tested against tirzepatide in a controlled trial. **Q: Is retatrutide FDA approved?** No. Retatrutide is investigational and not approved for use anywhere. Lilly plans to submit a Biologics License Application to the FDA in the first quarter of 2027; that filing has not yet occurred and approval is not guaranteed.