Eli Lilly has shared detailed data from a phase 3 retatrutide trial, revealing that more than one-third of patients on the top dose of the triple-G drug candidate lost at least 25% of their body weight.
Lilly reported topline data from the trial, Triumph-2, in July. The drugmaker shared a detailed look at the data on Tuesday at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan and in The Lancet. This week’s update provides a fuller picture of how 1,152 adults with obesity and Type 2 diabetes responded to retatrutide, an agonist of GIP, GLP-1 and glucagon receptors.
As previously reported, mean weight loss on the top, 12 mg dose was 20.8% at Week 80, versus a 4% dip on placebo. The fall in A1C from a baseline of 7.7% was 1.4% to 1.6% across the three retatrutide doses, compared to 0.2% for placebo. Lilly saw no dose-dependent effect on A1C, a measure of blood sugar. The analyses cover patients who stayed on treatment without starting prohibited weight-management drugs.
Lilly’s latest update provides details beyond the topline primary and secondary endpoints. In the 12 mg arm, 34.9% of patients lost at least 25% of their body weight. Fifty-two per cent of patients lost at least 20% of their body weight. More than half of the patients no longer met the BMI criteria for obesity.
The results further differentiate retatrutide from tirzepatide, the market-leading GIP/GLP-1 drug that Lilly sells as Mounjaro and Zepbound. At Week 72 of a phase 3 trial, 34% of people receiving tirzepatide lost at least 20% of their body weight. Lilly didn’t include the proportion of patients who lost 25% of their body weight in the tirzepatide readout.
While retatrutide has reset the bar on weight loss, the expanded dataset adds to evidence that the drug candidate has a more modest effect on blood sugar. On the middle and top doses, 40% and 39.3%, respectively, of patients had A1C levels below 5.7%, putting them in the healthy range. In an earlier trial, up to 55.3% of patients receiving tirzepatide had A1C levels below 5.7%.
Lilly included cardiovascular risk factor data in the expanded retatrutide readout. At the top dose, Lilly saw average reductions of 39.5% in triglycerides, 19.6% in non-HDL cholesterol, 10.8 mmHg in systolic blood pressure, 6.7 inches in waist circumference and 58.3% in high-sensitivity C-reactive protein. The drugmaker reiterated the previously reported, GLP-1-like safety and tolerability profile.
Equipped with data from Triumph-2 and other trials, Lilly plans to file for FDA approval of retatrutide in the first quarter of next year. After seeing topline Triumph-2 data in July, Guggenheim Securities analysts said they had high confidence in a timely approval.
FDA approval would add another potential blockbuster to Lilly’s cardiometabolic disease franchise and limit rivals’ ability to compete by offering higher weight loss. Even so, rivals continue to circle. At EASD this week, researchers presented phase 1, Week 12 data on Hengrui Pharma and Kailera Therapeutics’ triple-G agonist that “looks better” than retatrutide, TD Cowen analysts said in a note to investors.