Lilly retatrutide doubles Ozempic weight loss in diabetes trial

Eli Lilly’s investigational medicine retatrutide has not been approved by the U.S. Food and Drug Administration or any other regulator, the company said, but in a phase 3 study that enrolled more than 1,000 patients with type 2 diabetes it produced more than twice the weight loss of Novo Nordisk’s approved GLP-1 drug Ozempic (semaglutide).

The trial, called TRANSCEND-T2D-2, lasted 80 weeks and compared retatrutide 9 mg and 12 mg with Ozempic’s maximum approved dose of 2 mg. At week 80, participants lost an average of 44.3 pounds on the 9 mg dose and 47.4 pounds on the 12 mg dose, versus 20.9 pounds for Ozempic, ABC News reported. Those declines equaled 19.5% and 20.9% of body weight for retatrutide and 9.4% for Ozempic, according to pharmaphorum.

Retatrutide also lowered A1C, a marker of blood sugar control, by 2.2% with both doses, compared with 1.8% for Ozempic 2 mg. The medicine was linked to better heart-related measures, including cholesterol and blood pressure, ABC News reported.

The once-weekly injection targets three hormones: GLP-1, GIP and glucagon. Ozempic acts only on GLP-1; Lilly’s Mounjaro and Zepbound target GLP-1 and GIP. Glucagon, the third hormone, helps break down stored fat into energy, Business Insider reported.

Side effect profiles were generally similar between the two drugs, but diarrhea was slightly more common with retatrutide and constipation with Ozempic. Retatrutide also had a slightly higher rate of dysesthesia, a rare side effect involving tingling or skin-burning sensations.

Lilly plans to submit retatrutide for FDA approval in early 2027, and if approved it could become available next year, according to Business Insider. The drug may be used for obesity, obesity-related sleep apnea and knee osteoarthritis, if cleared, the outlet said. Lilly Cardiometabolic’s president, Kenneth Custer, stated in a company release, “We believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions.” The company added that retatrutide has no marketing approval from the FDA or any other regulator and that selling it to consumers is illegal.

Lilly already dominates the incretin market through tirzepatide, sold as Mounjaro and Zepbound, which contributed $27.7 billion of the company’s $42.8 billion first-half revenue, pharmaphorum reported. The study is the first phase 3 trial of retatrutide to compare it directly with another incretin medicine, and it is the sixth late-stage study of the triple agonist to report strong efficacy, according to pharmaphorum. Analysts have forecast peak annual sales of $10 billion to $25 billion, increasing pressure on Novo Nordisk, whose CagriSema has had less impressive results, the outlet said. Business Insider reported that the findings have not yet undergone peer review or appeared in a medical journal.