Patients treated in a Phase II study with Lilly’s retatrutide saw up to 24% weight loss at 48 weeks, driven by a triagonist mode of action that can bind and activate the GLP-1, GIP and glucagon receptors.
Pictured: Red Lilly sign on a white board, sitting on top of a brick tower/Getty Images, Cristina Arias
New Phase II data show that Eli Lilly’s investigational triple agonist retatrutide induced up to 24% weight loss after 48 weeks in adults with overweight or obesity but without diabetes, the company announced Monday.
Patients given the highest retatrutide dose of 12 mg lost nearly 58 pounds on average, corresponding to a 24.2% mean weight reduction after 48 weeks of treatment. At the lowest dose levels of 1 mg and 4 mg, retatrutide treatment still led to an 8.7% and 17.1% mean weight loss at this time point, respectively.
These findings were published in the New England Journal of Medicine on Monday, and the data were presented simultaneously at the American Diabetes Association scientific sessions in San Diego.
Study participants “had not yet reached a weight plateau at the time the study ended,” Ania Jastreboff, director of the Yale Obesity Research Center, said in a press release statement, suggesting that retatrutide has still not reached its full weight loss efficacy.
“Longer duration Phase III trials will enable a comprehensive evaluation of efficacy and tolerability of this potential pharmacotherapeutic for the treatment of obesity,” Jastreboff said.
Retatrutide is an investigational peptide that can bind and activate three receptors: the GLP-1, GIP and glucagon receptors. This triagonist mode of action allows retatrutide to induce the glucose-dependent insulin release from the pancreas via GLP-1 receptors, enhance this GLP-1-mediated effect through GIP receptors, and increase energy expenditure through glucagon receptors.
Lilly’s Phase II study was a double-blinded, randomized and placebo-controlled trial that enrolled 338 obese adults or those who were overweight and had at least one weight-related condition. Retatrutide was dosed subcutaneously at four doses: 1 mg, 4 mg, 8 mg and 12 mg. Patients in the 4-mg- and 8-mg groups were divided into two and given initial doses of 2 mg or 4 mg.
The study’s primary outcome was mean weight loss after 24 weeks. Compared with placebo, retatrutide treatment resulted in average weight reduction ranging from 7.2% in the lowest dose group to 17.5% in the highest. Lilly’s candidate also improved the study’s exploratory cardiometabolic endpoints, including total cholesterol, HbA1c, blood pressure, fasting glucose and insulin.
In the study, retatrutide’s safety profile was similar to other incretin-based treatments. The most common side effects were gastrointestinal, with mostly mild or moderate in severity. Retatrutide’s adverse events were also dose-dependent and could be partially mitigated using a lower starting dose.
With these promising mid-stage data, Lilly will continue evaluating retatrutide’s weight loss potential in the Phase III TRIUMPH clinical development program, which includes four core registrational studies.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
