The ‘Godzilla’ of weight-loss drugs could offer other important health benefits | Weight loss drugs

The “Godzilla” of weight-loss drugs could help improve blood sugar levels, reduce inflammation and cut a person’s 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 medications such as Wegovy, which primarily targets the GLP-1 pathway to suppress appetite, or Mounjaro, which contains GLP-1 and GIP to control blood sugar, retatrutide also engages the glucagon receptor, which helps increase energy expenditure.

The drug has not yet been approved by any regulatory body. But results from the global trial of people with obesity and type 2 diabetes suggest it could help them shed huge amounts of excess weight while providing other important health benefits.

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

The results of the study, funded by retatrutide maker Eli Lilly, were published in the medical journal Lancet and presented at the annual meeting of the European Association for the Study of Diabetes in Milan, Italy.

The randomized, double-blind, placebo-controlled trial enrolled 2,047 adults in eight countries: Argentina, Australia, Brazil, India, Mexico, Romania, Spain and the United States.

Participants had a body mass index (BMI) of 27 or more and type 2 diabetes. 48% were women and 52% men. Their average age was 55 years old.

During the 80-week phase 3 trial, 1,152 people were randomly assigned to receive a weekly injection of placebo (289) or retatrutide 4 mg (292), 9 mg (284), or 12 mg (287), along with dietary advice and advice on physical activity.

At the end of the study, those taking 4 mg of retatrutide lost an average of 11.9% of their body weight, increasing to 16.8% with 9 mg and 18.8% with 12 mg. Those in the placebo group lost 5.1%.

Of those who received the 12 mg dose, almost half (47%) lost at least 20% of their initial weight and almost a third (31%) lost at least 25%. This compares to 6% and 3% respectively with the placebo.

Additionally, 72% achieved an HbA1c (measuring average blood sugar levels over the past two to three months) of 6.5% or less, a standard threshold used to diagnose type 2 diabetes, compared to 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. Diarrhea occurred in 27 to 34% of participants in the retatrutide groups, compared to 13% in the placebo group, and nausea occurred in 14 to 28% of participants on retatrutide, compared to 8% in the placebo group.

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

Meanwhile, separate research presented at the Milan conference and published in the medical journal Lancet Obstetrics, Gynecology & Women’s Health showed that in most cases, weight-loss medications are not associated with adverse pregnancy outcomes in women living with type 2 diabetes.

But the researchers stressed that more research was urgently needed to fill large evidence gaps and keep pace with the huge and accelerating increase in the number of women of childbearing age using these drugs.