Triple‑agonist: big weight drops
A triple‑agonist obesity drug, retatrutide, produced very large average weight loss in a phase‑3 trial — reported at roughly an average of 71.2 pounds — and was also linked to reduced osteoarthritis pain in the study summary (PharmExec reports phase‑3 data). (pharmexec.com) The same coverage notes these drugs act on three receptors (GLP‑1, GIP and glucagon), and commentators are exploring liver‑disease benefits alongside weight loss in early analyses. (ajmc.com)
Retatrutide, an experimental Eli Lilly obesity drug, cut body weight by an average 28.7% in a phase 3 trial, or about 71.2 pounds. (lilly.com) Lilly released those topline TRIUMPH-4 results on December 11, 2025, in adults with obesity or overweight, knee osteoarthritis, and no diabetes. Patients on the 12-milligram weekly dose also saw WOMAC pain scores fall by an average 4.5 points, or 75.8%, after 68 weeks. (lilly.com) The drug is called a triple agonist because it activates three hormone receptors at once: glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon. In plain terms, those signals affect appetite, blood sugar, and energy use, and Lilly describes retatrutide as a once-weekly injectable treatment. (nejm.org; lilly.com) Retatrutide is still investigational, not an approved medicine, and Lilly has more phase 3 studies underway in obesity and type 2 diabetes. In a separate phase 3 diabetes trial released March 19, 2026, Lilly said patients on the 12-milligram dose lost an average 36.6 pounds, or 16.8%, at 40 weeks. (lilly.com; lilly.com) The numbers are larger than the weight-loss figures Lilly reported from retatrutide’s mid-stage study in 2023. In that phase 2 trial, published in The New England Journal of Medicine on June 26, 2023, the 12-milligram group reached an average 24.2% weight reduction at 48 weeks. (nejm.org) The osteoarthritis result puts weight loss and joint symptoms in the same study. Lilly said more than 1 in 8 retatrutide-treated patients were completely free from knee pain by the end of TRIUMPH-4, and 84.0% of participants started with a body-mass index of at least 35. (lilly.com) Liver disease is the next front in the same drug class. A Nature Medicine paper published June 10, 2024, reported that retatrutide reduced liver fat by 81.4% to 82.4% at the 8-milligram and 12-milligram doses after 24 weeks in a phase 2a study of patients with metabolic dysfunction-associated steatotic liver disease. (pmc.ncbi.nlm.nih.gov) Lilly has already moved that question into a large outcomes study. ClinicalTrials.gov says the phase 3 SYNERGY-OUTCOMES trial, updated March 20, 2026, is recruiting about 4,500 adults to test whether retatrutide and tirzepatide can prevent major adverse liver outcomes in high-risk metabolic dysfunction-associated steatotic liver disease. (clinicaltrials.gov) What comes next is less about one headline number than whether the rest of Lilly’s phase 3 program holds up across obesity, diabetes, joints, and liver disease. For now, TRIUMPH-4 is the company’s first successful phase 3 obesity readout for retatrutide, and the biggest average weight-loss figure Lilly has reported for the drug. (lilly.com; lilly.com)
