An experimental drug helped people with Type 2 diabetes lose more than one-fifth of their body weight in a clinical trial. That’s all the more impressive because it targets a group that has historically struggled to achieve substantial weight loss, even with medication.

The drug, retatrutide, developed by Eli Lilly, produced an average weight reduction of 20.8% over 80 weeks at its highest dose. It also significantly improved blood sugar control, with roughly 40% of participants on the two highest doses achieving blood sugar levels within the normal range.

The findings suggest that targeting three different hormone receptors simultaneously could offer a powerful new way to treat obesity and diabetes together.

The findings come from TRIUMPH-2, a Phase 3 clinical trial involving 1,152 adults with Type 2 diabetes and obesity or overweight. Participants received weekly injections of retatrutide at target doses of 4 mg, 9 mg or 12 mg, or a placebo. All groups also received guidance on diet and physical activity.

After 80 weeks, participants receiving the highest dose lost an average of 49.6 pounds (22.5 kilograms), equivalent to 20.8% of their initial body weight. Those receiving 9 mg lost 19.1%, while the 4 mg group lost 12.7%. Participants receiving placebo lost 4%.

These figures estimate weight loss if participants had continued treatment as planned. A separate analysis accounting for treatment discontinuation and other changes found a slightly different 18.8% average reduction with 12 mg, compared with 5.1% for placebo.

The results were especially notable among participants who started with a body mass index (BMI) of at least 35, a level classified as class II obesity. By the end of the trial, 59.5% of participants on the highest dose no longer met the BMI threshold for obesity.

Beyond weight loss, participants saw an average reduction of around 1.6 percentage points in HbA1c, a measure of average blood sugar levels over approximately three months.

That may not sound like much, but let’s put it this way: even at the 9 mg dose, 40% of participants achieved an HbA1c below 5.7%, compared with just 4.4% in the placebo group. That threshold is basically the normal blood sugar range.

Persistently elevated blood sugar can damage blood vessels and nerves, increasing the risk of kidney disease, vision problems and cardiovascular complications. The drug appears to target all of

There’s another reason why the drug is promising.

Losing weight is particularly challenging for people with Type 2 diabetes. Insulin resistance, metabolic changes and certain diabetes medications can seriously hamper a patient’s efforts to lose weight. Even successful obesity drugs have generally produced smaller weight reductions in people with diabetes than in those without it.

Retatrutide belongs to the same broad family of treatments as Ozempic and Mounjaro, but it works differently.

Semaglutide, the active ingredient in Ozempic and Wegovy, mimics a gut hormone called GLP-1, which helps regulate blood sugar, slows stomach emptying and reduces appetite. Tirzepatide, sold as Mounjaro and Zepbound, acts on two hormone receptors: GLP-1 and GIP.

Retatrutide goes a step further by activating a third receptor, for glucagon.

Glucagon normally helps raise blood sugar by signaling the liver to release glucose. That might seem counterproductive in people with diabetes. However, activating glucagon receptors may also increase energy expenditure, potentially helping the body burn more calories.

By combining glucagon’s metabolic effects with the appetite and blood sugar benefits of GLP-1 and GIP, researchers hope to achieve greater weight loss without sacrificing glucose control.

However, side effects remain a problem.

Among participants receiving 12 mg, 33.6% experienced diarrhea, 28% reported nausea and 15.7% experienced vomiting. These are very common side effects and they’re not pleasant at all. In the placebo group, those rates were 13.2%, 8% and 4.2%, respectively. Researchers note that 7.7% of participants couldn’t complete the study because of side effects.

Still, for people managing both obesity and Type 2 diabetes, retatrutide raises the possibility of achieving substantial weight loss and better blood sugar control with a single weekly treatment. For some, that would be worth the side effects.

Whether that promise translates into lasting improvements in health will depend on evidence that extends well beyond the scale.

Researchers presented the results at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan, Italy, and simultaneously published them in The Lancet.

Primary source: Bellido V. et al. (2026), Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2), The Lancet. DOI: 10.1016/S0140-6736(26)01861-1.