The ‘Godzilla’ of weight-loss drugs could help improve blood sugar levels, reduce inflammation and cut a person’s body weight by a quarter, according to the largest study of its kind. Retatrutide mimics three key gut hormones that help control appetite, blood sugar and metabolism: GLP-1, GIP and glucagon. Unlike other drugs such as Wegovy, which primarily targets the GLP-1 pathway to suppress appetite, or Mounjaro, which contains GLP-1 plus GIP to control blood sugar levels, retatrutide also engages the glucagon receptor, which helps increase energy expenditure.
The drug has not yet been approved by any regulatory agency. But the results of the global trial in people living with obesity and type 2 diabetes suggest it could help them shift enormous amounts of excess weight while also providing other important health benefits. The findings from the study, funded by retatrutide maker Eli Lilly, were published in the Lancet medical journal and presented at the annual meeting of the European Association for the Study of Diabetes in Milan, Italy.
The randomised, double-blind, placebo-controlled trial enrolled 2,047 adults in eight countries: Argentina, Australia, Brazil, India, Mexico, Romania, Spain and the US. Participants had a body mass index (BMI) of 27 or above and type 2 diabetes. 48% were women and 52% were men. Their average age was 55.
In the 80-week phase 3 trial, 1,152 were randomly assigned to receive a weekly injection of placebo (289), or retatrutide 4 mg (292), 9 mg (284) or 12 mg (287), alongside dietary counselling and guidance on physical activity. By the end of the study, those on 4mg of retatrutide lost 11.9% of their body weight on average, increasing to 16.8% with 9mg and 18.8% on 12mg. Those in the placebo group lost 5.1%.
Among those on the 12 mg dose, almost half (47%) shed at least 20% of their starting weight and almost a third (31%) lost at least 25%. That compared with 6% and 3%, respectively, with placebo. Additionally, 72% achieved an HbA1c (measuring average blood sugar levels for the last two to three months) of 6.5% or lower, a standard threshold used to diagnose type 2 diabetes, compared with 29% in the placebo group.
Retatrutide also significantly improved cardiometabolic risk factors, including blood pressure and lipid profiles, and reduced high-sensitivity C-reactive protein (hsCRP), a marker of inflammation, according to the researchers. The most frequently reported adverse events were gastrointestinal. Diarrhoea occurred in 27-34% of participants in the retatrutide groups, compared with 13% in the placebo group, and nausea occurred in 14-28% of participants on retatrutide, compared with 8% receiving the placebo.
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