Eli Lilly and Company has reported positive Phase 3 trial results for its experimental obesity drug, retatrutide, indicating that patients achieved substantial weight reduction over two years of treatment. The findings position retatrutide as a significant addition to the company's robust obesity pipeline, which already includes the approved drug Zepbound.
In the TRIUMPH-1 study, participants who received the highest 12 mg dose of retatrutide experienced an average body weight loss of 28.3%, equivalent to 31.9 kg, over 80 weeks. An extension study involving patients with severe obesity saw average weight loss reach 30.3% (38.5 kg) over 104 weeks. Notably, 45.3% of participants on the 12 mg dose achieved at least 30% weight loss, and 65.3% moved below the obesity threshold of a BMI of 30 after 80 weeks.
How Retatrutide Works
Retatrutide represents a new class of obesity therapies, distinguishing itself by targeting three hormones crucial for appetite regulation, insulin secretion, and energy use: GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1), and glucagon. This triple-receptor agonism is believed by researchers to contribute to greater weight reduction compared to existing treatments like Lilly’s Zepbound, which targets GIP and GLP-1 receptors.
Trial Scope and Additional Benefits
The TRIUMPH-1 trial enrolled 2,339 adults who were either obese or overweight and had at least one weight-related health condition, though diabetes patients were excluded from this specific study. Beyond weight loss, the therapy also demonstrated improvements in various cardiometabolic indicators, including waist circumference, triglyceride levels, blood pressure, and inflammatory markers.
Ania Jastreboff, the lead investigator of the study, emphasized the need for diverse treatment options for obesity. “Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease,” Jastreboff stated.
Side Effects and Future Prospects
Commonly reported side effects included nausea, diarrhea, constipation, and vomiting, which Lilly noted were generally consistent with other incretin-based obesity medicines. Discontinuation due to adverse events was 11.3% in the 12 mg group, compared to 4.9% for the placebo group.
Detailed findings from the study are slated for presentation at the annual meeting of the American Diabetes Association next month. Eli Lilly is also actively investigating retatrutide’s potential in treating obesity linked to other conditions, such as diabetes, cardiovascular disease, sleep apnea, and fatty liver disease.