A next-generation weight-loss drug may cut body weight by nearly 30%

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Adults with obesity who took the highest 12 mg dose of retatrutide lost an average of 28.3% of their body weight over 80 weeks in the TRIUMPH-1 Phase 3 trial, Eli Lilly reported.

That works out to roughly 70 pounds. The full results were presented at the American Diabetes Association's 86th Scientific Sessions in June 2026.

Retatrutide is an investigational once-weekly injection from Eli Lilly. It is a triple hormone receptor agonist, acting on the GLP-1, GIP, and glucagon receptors. Existing weight-loss drugs hit one or two of those targets.

The randomized, double-blind trial enrolled 2,339 adults with obesity, or with overweight plus at least one weight-related complication. Participants received placebo or one of three retatrutide doses. All three doses beat placebo on the primary endpoint.

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How it stacks up against Ozempic and Zepbound

In the 72-week SURMOUNT-5 head-to-head trial of 751 adults with obesity, tirzepatide produced a 20.2% mean weight loss and semaglutide 13.7%.

Tirzepatide is the active ingredient in Eli Lilly's Mounjaro and Zepbound. Semaglutide is the active ingredient in Novo Nordisk's Ozempic and Wegovy.

Retatrutide's 28.3% at 80 weeks sits several points above tirzepatide, and roughly double the semaglutide figure. Pharmaceutical Technology called it the most efficacious pharmacological agent for obesity reported to date in a Phase III setting.

At the top dose, 45.3% of participants lost at least 30% of their body weight, a threshold long associated with bariatric surgery. More than 65% ended the trial no longer meeting the clinical definition of obesity.

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"Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease," said Ania Jastreboff, MD, PhD, director of the Yale Obesity Research Center, in the company's release.

Side effects looked similar to other GLP-1 drugs

The side effect profile fell in line with existing GLP-1 medicines. Nausea, diarrhea, constipation, and vomiting were the most common complaints, and most were mild to moderate.

In the 12 mg group, 42.4% reported nausea and 25.3% reported vomiting, compared with 14.8% and 4.8% in the placebo group.

Discontinuation because of side effects rose with dose, reaching 4.1% at 4 mg, 6.9% at 9 mg, and 11.3% at 12 mg.

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A prespecified extension out to 104 weeks in participants with a starting BMI of at least 35 showed continued weight loss, reaching 30.3% at the top dose.

Retatrutide has not yet been approved by the Food and Drug Administration. Anyone considering treatment for obesity, including current GLP-1 users, should talk with their doctor about the options.

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This article is made and published by Jesper Bengtson, who may have used AI in the preparation.

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