‘Godzilla’ weight loss drug shows significant potential in other areas – study

A phase 3 retatrutide trial found reduced body weight, improved blood sugar and lower inflammation markers in adults with obesity and type 2 diabetes.

The drug, which is not yet approved by any regulatory agency, mimics three gut hormones involved in appetite, blood sugar and metabolism: GLP-1, GIP and glucagon.

Unlike drugs that target GLP-1 alone or GLP-1 and GIP, retatrutide also activates the glucagon receptor, which helps increase energy expenditure.

The randomised, double-blind, placebo-controlled trial enrolled 2,047 adults across Argentina, Australia, Brazil, India, Mexico, Romania, Spain and the US. Participants had a body mass index of at least 27 and type 2 diabetes.

The research was funded by Eli Lilly, the maker of retatrutide, and presented at the annual meeting of the European Association for the Study of Diabetes in Milan.

Of those enrolled, 1,152 participants in the 80-week phase 3 trial were randomly assigned to receive a weekly injection of placebo or retatrutide at doses of 4 mg, 9 mg or 12 mg, alongside dietary counselling and physical activity guidance.

Participants receiving 4 mg lost an average of 11.9 per cent of their body weight, compared with 16.8 per cent among those receiving 9 mg and 18.8 per cent in the 12 mg group. The placebo group lost 5.1 per cent.

Among participants receiving 12 mg, 47 per cent lost at least 20 per cent of their starting weight and 31 per cent lost at least 25 per cent. This compared with 6 per cent and 3 per cent respectively in the placebo group.

Researchers also reported improvements in blood sugar control. In the retatrutide groups, 72 per cent achieved an HbA1c of 6.5 per cent or lower, compared with 29 per cent in the placebo group.

HbA1c measures average blood sugar levels over the previous two to three months.

Retatrutide also significantly improved cardiometabolic risk factors, including blood pressure and lipid profiles, and reduced high-sensitivity C-reactive protein, or hsCRP, a marker of inflammation.

The researchers said: “Retatrutide demonstrated substantial reduction in body weight alongside glycaemic control and cardiometabolic risk factors, with a safety profile generally similar to other molecules with GLP-1 receptor agonist activity.”

The most frequently reported adverse events were gastrointestinal.

Diarrhoea occurred in 27 to 34 per cent of participants receiving retatrutide, compared with 13 per cent in the placebo group. Nausea affected 14 to 28 per cent of participants taking retatrutide, compared with 8 per cent receiving placebo.

Seven deaths occurred during the trial: two in the 4 mg retatrutide group, three in the 9 mg group, one in the 12 mg group and one in the placebo group. Investigators deemed the deaths unrelated to the study intervention.