Lilly's obesity triple pulls off 29% weight loss in trial

Eli Lilly has ramped up the competition in weight-loss therapies by reporting the first pivotal data with its triple therapy retatrutide, showing average weight losses of up to 28.7% in its first phase 3 readout.

Top-line results from the TRIUMPH-4 trial, carried out in patients overweight or with obesity and knee osteoarthritis, raise expectations for the prospects of retatrutide, which targets GLP-1, GIP, and glucagon with a single once-weekly subcutaneous injection.

The 28.7% weight reduction with the higher, 12 mg dose of retatrutide, recorded after 68 weeks of treatment, was accompanied by a 75.8% reduction in knee osteoarthritis pain measured using the WOMAC scale.

The results also revealed significantly improved measures of physical function, with more than one out of eight retatrutide-treated patients completely free from knee pain at the end of the trial, according to Lilly. Moreover, the lower 9 mg dose of retatrutide tested in the study also performed well, with a 26.4% reduction in weight at 68 weeks compared to a 2.1% fall in the placebo group.

Nearly a quarter (23.7%) of patients on retatrutide 12 mg achieved weight loss of 35% or more, setting a new standard for obesity therapies. However, approximately 18% of patients on the highest dose of the drug stopped treatment due to side effects, compared with 4% of those in the placebo group, so, tolerability could be something to watch in future readouts.

Overall, the results achieved with the drug appear to have exceeded analyst expectations, and Lilly's share price rose more than 1% in premarket trading.

The strong result looks likely to increase the pressure on Lilly's main rival in the obesity space, Novo Nordisk, which is already coming under pressure from Lilly's dual-acting GIP/GLP-1 agonist Zepbound (tirzepatide).

"We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide," said Kenneth Custer, president of Lilly Cardiometabolic Health, in a statement.

"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 retatrutide also includes studies of people who are overweight or obese and also 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, such as heart attack, glaucoma, diabetes, cancer, and cognitive and behavioural disorders.

News of the retatrutide broke shortly after Lilly was linked in unconfirmed reports to a possible takeover bid for French biotech Abivax and its lead drug obefazimod, a treatment for ulcerative colitis, which achieved positive results in a phase 3 trial earlier this year.