'Godzilla' weight-loss drug retatrutide may offer wider health benefits, major trial finds

A major global trial published in The Lancet and presented at the European Association for the Study of Diabetes annual meeting in Milan has found that the experimental drug retatrutide can produce substantial weight loss alongside other health improvements in people with obesity and type 2 diabetes.

Unlike existing drugs such as Wegovy, which targets only the GLP-1 pathway, or Mounjaro, which combines GLP-1 and GIP, retatrutide acts on three hormone receptors — GLP-1, GIP and glucagon. The glucagon receptor activity is thought to help increase energy expenditure. The drug is made by Eli Lilly, which funded the study, but it has not yet been approved by any regulatory agency.

Trial results

The randomised, double-blind, placebo-controlled phase 3 trial ran for 80 weeks and enrolled 2,047 adults across eight countries, including the US, Spain and India. Of these, 1,152 participants, with an average age of 55, received weekly injections of either placebo or one of three retatrutide doses, alongside dietary and activity guidance.

Participants on the 4mg dose lost an average of 11.9% of body weight, those on 9mg lost 16.8%, and those on the highest 12mg dose lost 18.8%, compared with 5.1% in the placebo group. Among those on the highest dose, nearly half lost at least 20% of their starting weight. Additionally, 72% of participants on the highest dose achieved healthy blood sugar levels, compared with 29% on placebo, and the drug also improved blood pressure, cholesterol levels and markers of inflammation.

The most common side effects were gastrointestinal, including diarrhoea and nausea, which occurred significantly more often in the retatrutide groups than with placebo. Seven deaths were recorded during the trial, all judged by investigators to be unrelated to the treatment.

Separate research presented at the same conference found that weight-loss drugs were generally not linked to adverse pregnancy outcomes in women with type 2 diabetes, though researchers said more research is urgently needed given the rapidly growing number of women of reproductive age using such medications.