Eli Lilly's Retatrutide Shows 28.7% Weight Loss in New Trials—but at a Cost

Eli Lilly has announced plans for seven more Phase III trials of retatrutide in 2025. The drug, which targets three metabolic receptors, has shown significant weight-loss results in recent studies. New data reveals both its high effectiveness and some tolerability challenges for patients.

Retatrutide works by activating receptors for GLP-1, GIP, and glucagon. Early Phase II results in the TRIUMPH-2 study showed a 17.5% average weight loss at 24 weeks with a 12-mg dose. Later, the Phase III TRIUMPH-4 trial extended this to 28.7% (32 kg) over 68 weeks at the same dose.

The TRIUMPH-4 trial involved 445 adults with obesity or overweight. Participants received either 9 mg, 12 mg of retatrutide, or a placebo once weekly. Those with a BMI of 35 or higher had fewer dropouts—8.8% on 9 mg and 12.1% on 12 mg.

However, side effects led more patients to stop treatment in the retatrutide groups. Around 18.2% discontinued at the 12-mg dose, compared to 12.2% on 9 mg. A notable side effect, dysesthesia, affected roughly 20% of those on the higher dose.

Despite tolerability concerns, the drug's weight-loss results outpaced earlier trials. The 12-mg dose in TRIUMPH-4 surpassed the 24.2% loss seen in Phase II at 48 weeks. Patients starting at 112.7 kg lost an average of 32.3 kg by the trial's end.

Eli Lilly is moving forward with seven additional Phase III trials next year. The company will also explore a 4-mg maintenance dose of retatrutide. While the drug delivers substantial weight loss, its side effects may limit use to patients needing deeper metabolic benefits.