Eli Lilly announced a significant milestone for its next-generation obesity drug, retatrutide, which has successfully completed its first late-stage trial focused on Type 2 diabetes patients. The trial demonstrated the drug’s effectiveness in managing blood sugar levels and aiding weight loss among participants. Specifically, retatrutide lowered hemoglobin A1c—an essential measure of blood sugar—by an average of 1.7% to 2% across various dosages at the 40-week mark, surpassing the study’s primary endpoint. Patients enrolled in the trial had A1c levels ranging from 7% to 9.5% and were not on any other diabetes medications at the start of the study.
In addition to its effects on blood sugar, the highest dosage of retatrutide helped participants lose an average of 16.8% of their body weight, equivalent to approximately 36.6 pounds, during the 40-week period for those who remained on the drug. When considering the entire participant group, including those who dropped out, the same dosage resulted in a weight loss of 15.3%.
Ken Custer, president of Lilly Cardiometabolic Health, expressed enthusiasm over the drug’s dual impact on reducing blood sugar and achieving substantial weight loss, especially considering the historical challenges faced by Type 2 diabetes patients in managing their weight. The trial also reported relatively low discontinuation rates due to side effects, which stood at about 5%.
This marks the second late-stage trial for retatrutide, which operates through a unique mechanism compared to existing injectable treatments. Eli Lilly is positioning retatrutide as a cornerstone of its obesity treatment portfolio, alongside its celebrated weight-loss injection Zepbound and an upcoming oral medication, orforglipron. However, the company has yet to submit a formal request for regulatory approval for either obesity or diabetes indications. Additional results from seven other phase three trials on retatrutide are expected to be released by the end of the year.
Comparatively, while retatrutide’s A1C reduction is robust, it appears to be slightly below what Lilly achieved with Zepbound, which lowered A1c by more than 2% in previous studies involving diabetes patients. Nonetheless, Custer emphasized that retatrutide’s performance is still commendable relative to diabetes medications that do not focus on gut hormones.
Lilly aims to provide varied treatment options in the obesity and diabetes markets, recognizing that patients may have different needs and preferences for medications. For those prioritizing blood sugar control, either Zepbound or retatrutide may be suitable; however, for those primarily seeking weight loss, retatrutide may provide a competitive advantage.
Retatrutide has showcased a safety profile akin to other injectable diabetes and obesity therapies, with gastrointestinal side effects being the most commonly reported. Approximately 26.5% of individuals experienced nausea, while rates of diarrhea and vomiting were 22.8% and 17.6%, respectively. Instances of dysesthesia, a nerve sensation discomfort, were notably low.
Characterized as the “triple G” drug, retatrutide mimics three hunger-regulating hormones—GLP-1, GIP, and glucagon—offering potentially more significant appetite control and satisfaction than some existing treatments, which often target only one or two pathways. For instance, tirzepatide in Zepbound addresses GLP-1 and GIP, while Novo Nordisk’s semaglutide focuses solely on GLP-1.
As retatrutide approaches market readiness, Novo Nordisk is actively developing competitive therapies. In March 2025, Novo announced a $2 billion agreement to acquire rights to an experimental weight-loss drug from Chinese firm United Laboratories International, which utilizes a similar approach to retatrutide. However, that treatment is still at an early development stage, suggesting it may take years before it becomes available to patients.
