Retatrutide shows promising results in weight and glucose reduction in phase 3 trial

A new triple-hormonal drug, retatrutide, demonstrates substantial weight loss and improved blood glucose control in its largest trial to date, signalling potential for a breakthrough in obesity and type 2 diabetes treatment, though regulatory approval is still pending.

Retatrutide, an experimental obesity drug that has drawn attention as one of the most powerful weight-loss candidates in development, produced substantial reductions in body weight and blood glucose in its largest trial so far, according to findings presented at the annual meeting of the European Association for the Study of Diabetes in Milan. The drug, however, is still not approved by any regulator for routine use. Reuters reported that the study involved adults with type 2 diabetes and added to earlier evidence that the treatment may do more than suppress appetite.

The treatment belongs to a newer class of medicines designed to act on three hormonal pathways at once: GLP-1, GIP and glucagon. That distinguishes it from semaglutide, the active ingredient in Wegovy, which mainly targets GLP-1, and tirzepatide, the active ingredient in Mounjaro, which works through GLP-1 and GIP. By also activating the glucagon receptor, retatrutide is intended to influence energy use as well as appetite and glucose control. The triple-action approach has been central to the drug’s appeal in early studies and in the broader race to develop more effective treatments for obesity and diabetes.

In the phase 3 trial, 2,047 adults with type 2 diabetes from eight countries took part, all with a body-mass index of at least 27. The cohort was 48% female, 52% male and had a mean age of 55. A subgroup of 1,152 participants was randomly assigned to receive placebo or one of three weekly doses of retatrutide for 80 weeks, alongside advice on diet and physical activity. By the end of the study, people on the 4mg dose had lost an average of 11.9% of their body weight, while those on 9mg and 12mg lost 16.8% and 18.8% respectively. The placebo group lost 5.1%.

The highest dose also produced the largest share of major weight-loss responses. In the 12mg group, 47% of participants lost at least 20% of their starting weight and 31% lost at least 25%, compared with 6% and 3% in the placebo group. Blood sugar control improved as well: 72% of those taking retatrutide reached an HbA1c of 6.5% or lower, a common diagnostic threshold for type 2 diabetes, versus 29% in the placebo arm. The researchers said the drug also improved cardiovascular risk markers, including blood pressure and lipid levels, while reducing high-sensitivity C-reactive protein, a marker of inflammation.

Safety findings were broadly in line with the known profile of GLP-1-based medicines, although digestive side-effects were common. Diarrhoea affected 27% to 34% of people taking retatrutide, compared with 13% on placebo, while nausea was reported in 14% to 28% of treated participants and 8% of those on placebo. Seven deaths occurred during the trial, but the lead investigator did not link any of them to the study drug. Separate evidence cited alongside the trial, including a paper in The Lancet Obstetrics, Gynaecology & Women’s Health, suggested that weight-loss medicines were not usually associated with adverse pregnancy outcomes in women with type 2 diabetes, though researchers called for further work, particularly as use of these drugs rises among women of child-bearing age. Earlier phase 2 studies published in JAMA and the New England Journal of Medicine had already shown striking weight loss, helping to establish retatrutide as one of the most closely watched obesity drugs in development.