Eli Lilly’s triple-action obesity drug delivers striking weight-loss results in phase 3 trial
Eli Lilly has intensified the battle for dominance in the weight-loss market after unveiling the first pivotal data for its triple-hormone therapy retatrutide, which achieved average weight reductions of nearly 29 per cent in a phase 3 study.
Top-line results from the TRIUMPH-4 trial, conducted in people who were overweight or living with obesity and knee osteoarthritis, suggest strong prospects for the once-weekly injectable drug, which targets GLP-1, GIP and glucagon simultaneously.
The highest 12 mg dose of retatrutide delivered a 28.7 per cent reduction in weight after 68 weeks, alongside a 75.8 per cent decrease in knee osteoarthritis pain measured using the WOMAC scale. The findings surpassed many analyst forecasts, prompting Lilly’s share price to rise by more than one per cent in pre-market trading.
The robust data increase competitive pressure on Lilly’s main rival, Novo Nordisk, which is already contending with the success of Zepbound (tirzepatide), Lilly’s dual-acting GIP/GLP-1 therapy.
“We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide,” said Kenneth Custer, president of Lilly Cardiometabolic Health. “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.”
Lilly’s phase 3 programme for the drug also includes studies in people who are overweight or obese and have obstructive sleep apnoea (OSA), a condition for which Zepbound became the first FDA-approved treatment in December 2024. Untreated OSA can lead to serious complications including heart attack, glaucoma, diabetes, cancer and cognitive or behavioural disorders.
The results showed notable gains in physical function, with more than one in eight people treated with retatrutide reporting no knee pain by the end of the trial. The lower 9 mg dose also performed well, delivering a 26.4 per cent weight reduction over 68 weeks, compared with a 2.1 per cent fall in the placebo arm.
Nearly a quarter of those receiving the 12 mg dose achieved weight loss of at least 35 per cent, setting a new benchmark in obesity therapy outcomes. However, around 18 per cent of people on the highest dose discontinued treatment due to side effects, compared with four per cent on placebo, suggesting tolerability will remain a key consideration as further data emerge.