‘Godzilla’ of weight-loss drugs could provide other important health benefits

Retatrutide, a weight-loss drug currently under clinical trials but not yet approved by regulatory agencies, has shown promising results in studies. This "Godzilla" of weight-loss drugs could help improve blood sugar levels, reduce inflammation, and cut a person's body weight by up to a quarter. Unlike other drugs such as Wegovy and Mounjaro, retatrutide targets three key gut hormones - GLP-1, GIP, and glucagon - which control appetite, blood sugar, and metabolism.

The results from a global trial suggest that retatrutide could help obese individuals with type 2 diabetes lose substantial amounts of weight while providing other important health benefits. The researchers published the findings in the Lancet medical journal and presented them at the European Association for the Study of Diabetes meeting in Milan, Italy.

The trial enrolled over 2,000 adults from eight countries, with an average age of 55 and a body mass index (BMI) of 27 or above. Participants were randomly assigned to receive either a placebo or retatrutide injections (4 mg, 9 mg, or 12 mg) alongside dietary counseling and physical activity guidance.

The 80-week phase 3 trial showed that those on retatrutide lost significantly more weight than those on the placebo. By the end of the study, those on 12 mg of retatrutide lost an average of 18.8% of their body weight, compared to 5.1% in the placebo group. Additionally, 47% of participants on the 12 mg dose shed at least 20% of their starting weight, while 31% lost at least 25%.

Among those on placebo, only 6% and 3% achieved those weight loss milestones, respectively. Furthermore, 72% of participants on the 12 mg dose achieved an HbA1c level of 6.5% or lower, indicating better blood sugar control.

Retatrutide also improved cardiometabolic risk factors, including blood pressure and lipid profiles, and reduced high-sensitivity C-reactive protein (hsCRP), a marker of inflammation. The most common side effects were gastrointestinal, with diarrhoea occurring in 27-34% of participants on retatrutide versus 13% on placebo, and nausea in 14-28% on retatrutide versus 8% on placebo.

However, there were no deaths attributed to the study intervention. Meanwhile, separate research presented at the conference and published in the Lancet Obstetrics, Gynaecology & Women’s Health journal showed that weight-loss drugs are generally not associated with adverse pregnancy outcomes in women with type 2 diabetes, but more research is urgently needed to address the large evidence gaps and keep pace with the growing use of these drugs among women of reproductive age.