Twenty-six percent without diabetes lost at least 30% of body weight
Every person who escalated to receive the 8-mg or 12-mg weekly dose of retatrutide lost at least 5% of their bodyweight after 48 weeks, 83% of those taking the 12-mg dose lost at least 15%, 63% of those on the 12-mg dose lost at least 20%, and 26% of those on the highest dose lost at least 30% of their starting bodyweight, reported Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn.
The highest dose was also associated with an average 40% relative reduction in triglyceride levels from baseline and an average 22% relative drop in LDL cholesterol levels.
The results were simultaneously published online in the New England Journal of Medicine.
The incidence of serious adverse events with retatrutide was low, similar to the rate in those who received placebo, and showed no dose relationship.
The most common adverse events were gastrointestinal, in as many as 16% of those on the highest dose; these were mild to moderate in severity and usually occurred during dose escalation. In general, adverse events were comparable to what is seen with a GLP-1 agonist or the dual agonist tirzepatide, Dr. Jastreboff said.
A1c normalization in 26% at the highest dose
A similar safety pattern occurred in the study of people with type 2 diabetes, which randomized people with an average A1c of 8.3% and an average BMI of 35.0 kg/m2. After 36 weeks of treatment, the 12-mg weekly dose of retatrutide led to normalization of A1c < 5.7% in 27% of people and A1c ≤ 6.5% in 77%.
“The number of people we were able to revert to a normal A1c was impressive,” said Dr. Rosenstock. These results were simultaneously published online in The Lancet.
The additional findings on liver-fat mobilization in people without diabetes enrolled in the obesity study are notable because no agent currently has labeling from the Food and Drug Administration for the indication of reducing excess liver fat, said Dr. Kaplan.
The researchers measured liver fat at baseline and then during treatment using MRI.
“With the level of fat clearance from the liver that we see with retatrutide it is highly likely that we’ll also see improvements in liver fibrosis” in retatrutide-treated patients, Dr. Kaplan predicted.
Next up for retatrutide is testing in pivotal trials, including the TRIUMPH-3 trial that will enroll about 1,800 people with severe obesity and cardiovascular disease, with findings expected toward the end of 2025.
The retatrutide studies are sponsored by Eli Lilly. Dr. Jastreboff, Dr. Rosenstock, Dr. Kaplan, and Dr. Le Roux have reported financial relationships with Eli Lilly as well as other companies.
A version of this article first appeared on Medscape.com.