Eli Lilly’s retatrutide, a tirzepatide-related drug that mimics GLP-1, GIP and glucagon, helped adults with obesity and type 2 diabetes lose up to 18.8% of their body weight in an 80-week phase 3 trial. The results were published in Lancet and presented at the annual meeting of the European Association for the Study of Diabetes in Milan, Italy.
Participants on the 12 mg dose lost 18.8% of their body weight on average, compared with 16.8% on 9 mg, 11.9% on 4 mg and 5.1% in the placebo group. Among those on 12 mg, 47% shed at least 20% of their starting weight and 31% lost at least 25%.
Lancet and European Association for the Study of Diabetes
The randomised, double-blind, placebo-controlled study enrolled 2,047 adults from Argentina, Australia, Brazil, India, Mexico, Romania, Spain and the US. Participants had a body mass index of 27 or above and type 2 diabetes, with 48% women, 52% men and an average age of 55. In the trial, 1,152 participants were randomly assigned to placebo or retatrutide 4 mg, 9 mg or 12 mg, alongside dietary counselling and guidance on physical activity.
Retatrutide also improved blood sugar control. At the end of the study, 72% of participants on the drug reached an HbA1c of 6.5% or lower, compared with 29% in the placebo group. The drug also significantly improved blood pressure and lipid profiles and reduced hsCRP, a marker of inflammation.
Eli Lilly phase 3 trial
The safety findings were less clean. Diarrhoea affected 27-34% of participants in the retatrutide groups, versus 13% in the placebo group, and nausea occurred in 14-28% of those taking retatrutide, compared with 8% on placebo. Seven deaths occurred during the trial, including two in the 4 mg group, three in the 9 mg group, one in the 12 mg group and one in the placebo group.
The investigator said the deaths were unrelated to the study intervention. Retatrutide is not yet approved by any regulatory agency, leaving the practical question focused on whether the weight loss and blood sugar gains will be enough to carry the drug through the next step toward approval.
