A new weight-loss medication known as retatrutide has shown promising results in reducing body weight, improving blood sugar control, and lowering inflammation, according to a large international clinical trial. The drug, which mimics three gut hormones—GLP-1, GIP, and glucagon—targets appetite regulation, metabolism, and energy expenditure. Retatrutide’s mechanism distinguishes it from other weight-loss drugs like Wegovy and Mounjaro, which focus primarily on the GLP-1 and GIP pathways.
The phase 3 trial, the largest of its kind, involved 2,047 adults with obesity and type 2 diabetes across eight countries, including Argentina, Australia, Brazil, India, Mexico, Romania, Spain, and the United States. Participants had a body mass index (BMI) of 27 or higher and were nearly evenly split by gender, with an average age of 55. Over 80 weeks, participants received weekly injections of either a placebo or retatrutide at doses of 4 mg, 9 mg, or 12 mg, combined with dietary advice and physical activity guidance.
Results demonstrated a dose-dependent reduction in body weight. Participants on 4 mg lost an average of 11.9% of their body weight, compared with 16.8% on the 9 mg dose and 18.8% at 12 mg. By comparison, the placebo group experienced an average weight loss of 5.1%. Nearly half (47%) of those receiving the highest dose lost at least 20% of their starting weight, and 31% lost at least 25%, compared with 6% and 3% respectively in the placebo group.
In addition to weight loss, retatrutide significantly improved glycemic control. Approximately 72% of participants on retatrutide achieved an HbA1c level of 6.5% or below—a threshold commonly used for diagnosing type 2 diabetes—compared to 29% in the placebo group. The drug also reduced blood pressure, improved lipid profiles, and lowered levels of high-sensitivity C-reactive protein (hsCRP), a marker of inflammation.
The safety profile was generally consistent with other GLP-1 receptor agonists. Gastrointestinal side effects were the most common adverse events, with diarrhea reported in 27-34% of retatrutide-treated participants compared to 13% on placebo. Nausea affected 14-28% of those on retatrutide, versus 8% among placebo recipients. Seven deaths occurred during the trial across all groups, but investigators determined none were related to the study drug.
The trial, funded by Eli Lilly, has not yet led to regulatory approval of retatrutide but highlights the drug’s potential as a comprehensive treatment for people with obesity and type 2 diabetes.
Separately, research presented at the same conference examined the effects of weight-loss drugs on pregnancy outcomes for women with type 2 diabetes. The study found no significant association between these medications and adverse pregnancy results but emphasized the need for further research given the rising use of such drugs among women of reproductive age.