Lilly’s Next-Gen Obesity Shot Shows Best-In-Class Weight Loss In Study

Shares of Eli Lilly are higher in premarket trading after the company unveiled blowout topline results for its next-generation obesity drug retatrutide, which delivered more than 23% weight loss over 68 weeks – the strongest performance yet for a late-stage obesity trial.

Adult patients in the Phase 3 TRIUMPH-4 trial testing retatrutide, a first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist, entered the study with obesity or overweight and knee osteoarthritis. Most participants had a BMI of 35 or higher.

Result highlights for both high-dose regimens (9 mg and 12 mg):

• Met all primary and key secondary endpoints

• Produced massive weight loss: up to 28.7% on average (71.2 lbs) at 68 weeks

• Delivered major pain improvement: up to 4.5 points (75.8%) reduction on the WOMAC pain score

• Improved physical function, in addition to weight and pain outcomes

“We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide, a first-in-class triple agonist, on body weight, pain and physical function. With seven additional Phase 3 readouts expected in 2026, we believe retatrutide could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis,” Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health, wrote in a statement.

Some patients lost so much weight they chose to exit the trial early, particularly those with a BMI below 35. The highest dose saw an 18% dropout rate due to side effects, including nausea, diarrhea, constipation, and occasional mild dysesthesia.

“Not all patients may need this potentially very high level of efficacy, and we believe retatrutide will likely be best suited for patients with a very high BMI, or with obesity-related complications that require a high degree of weight loss,” Lilly’s Chief Scientific Officer Daniel Skovronsky told investors in October.

The results come as the race for next-generation obesity drugs intensifies: Shares of rival Novo Nordisk plummeted the most on record after an experimental GLP-1 fell short of Wall Street expectations last year. The drug CagriSema helped patients lose an average of 20.4% of their weight, far short of Novo’s promise.

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