Eli Lilly announced that retatrutide, a once-weekly triple hormone receptor agonist, produced an average weight loss of 28.3% (70.3 pounds) at the highest 12mg dose over 80 weeks among adults with obesity or overweight without diabetes [1, 2]. Approximately 45% of participants receiving the 12mg dose lost at least 30% of their weight during the trial period [1, 2].
The phase 3 trial enrolled roughly 2,339 to 2,500 participants with obesity or overweight and at least one weight-related condition, excluding diabetes [1, 2]. Those on 9mg and 4mg doses lost 25.9% (64.4 lbs) and 19.0% (47.2 lbs) respectively over the same period [1]. About 65% of patients on the 12mg dose reduced their BMI to below 30 after 80 weeks [1, 2].
Retatrutide activates GLP-1, GIP, and glucagon receptors, distinguishing it from other Eli Lilly drugs like Zepbound and Novo Nordisk's Wegovy, which are selective GLP-1 receptor agonists [1]. Typically, Zepbound users lose 15%-20% of their body weight over 72 weeks, while Wegovy users shed 14%-19% over 64 to 72 weeks [1].
An extension study showed patients with BMI above 35 lost an average of 30.3% of their weight over 104 weeks on the highest dose of retatrutide [2]. Compared with a placebo group, which saw only 2.2% weight loss, retatrutide demonstrated significantly greater efficacy [2].
Side effects included higher rates of gastrointestinal issues such as nausea and diarrhea at the highest dose, consistent with previous trials [2]. Dan Skovronsky, Lilly’s chief scientific and product officer, said, "We haven't seen that level of weight loss before with these kinds of medicines" [2]. Endocrinologist Dr. Susan Spratt called the results "the largest weight loss I've ever seen in any medication trial. This is huge" [1].
Eli Lilly announced the phase 3 results on May 21, 2026. Earlier in the year, retatrutide also succeeded in a diabetes trial. In December 2025, it cleared a smaller study in patients with obesity and knee arthritis [1, 2]. The company is expected to pursue regulatory review next.
