Eli Lilly's retatrutide shows significant weight loss and blood sugar improvements in Phase 3 trial

Eli Lilly reported new results from a Phase 3 trial of retatrutide, a drug that activates GLP-1, GIP and glucagon receptors. Participants received weekly injections of 4 mg, 9 mg or 12 mg and were followed for 80 weeks. Those on the 4-mg dose lost an average of 29.8 pounds, equivalent to 12.7% of their body weight. The 9-mg and 12-mg doses produced average weight losses of 45.4 pounds (19.1%) and 49.6 pounds (20.8%) respectively.

The study also documented improvements in glycemic control. On the lowest dose, average A1C fell by 1.4 percentage points, with larger reductions at higher doses. More than half of participants no longer met criteria for obesity, and up to 40% achieved normal-range A1C levels. Additional cardiovascular benefits were observed at the highest dose, including lower triglycerides, cholesterol, blood pressure, waist circumference and high-sensitivity C-reactive protein.

Side effects were consistent with other GLP-1 therapies, primarily gastrointestinal symptoms such as diarrhea (27.4%–33.6%), nausea, constipation, reduced appetite and vomiting, occurring more frequently at higher doses. Neurological sensations (dyesthesia) were reported in 4.5%–7.3% of participants, and urinary tract infections in 3.8%–8%, with severity generally mild to moderate and resolving during treatment.

"The vast majority of people with type 2 diabetes are also living with obesity, and treating the two together has always been a challenge," said Dr. Juan P. Frías, who led the research. "Retatrutide reduced both weight and blood sugar substantially, with more than half of participants no longer qualifying as having obesity and up to 40% reaching an A1C in the normal range."