Lilly's 'triple G' retatrutide aces crucial obesity trial
Eli Lilly's triple G agonist retatrutide has achieved weight loss of more than 28% in a new phase 3 trial that keeps it on course for regulatory filings later this year.
The readout from the TRIUMPH-1 study – in high-risk, obese patients with a body mass index (BMI) of 35 or more – revealed 28.3% weight loss at the highest dose of the GLP-1, GIP and glucagon agonist, 12 mg by injection once a week, compared to a 2.2% fall with placebo at 80 weeks.
There was also a dose response with retatrutide, with a 9 mg dose leading to a median weight loss of 25.9% from baseline and 4 mg coming in at 19%.
The weight loss was also accompanied by significant reductions in waist circumference, known to raise the risk of cardiovascular disease and other weight-related complications, and other cardiovascular risk factors, including non-HDL cholesterol, triglycerides, systolic blood pressure and C-reactive protein.
Moreover, a remarkable 45.3% of patients treated with retatrutide 12 mg achieved 30% or more weight loss, a level that Lilly said is typically seen in people undergoing bariatric surgery, and weight loss reached 30.3% at 104 weeks in people who were able to tolerate the 12 mg dose.
The strong result comes after Lilly posted equally impressive results with retatrutide in people living with overweight/obesity and knee osteoarthritis in the TRIUMPH-4 study, and in type 2 diabetes patients in the TRANSCEND-T2D-1 trial, building the case for the drug as one of the major new medications in the cardiometabolic category.
"It was impressive to see that every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants," commented lead TRIUMPH-1 investigator Ania Jastreboff, director of the Yale Obesity Research Centre.
"Treatment with retatrutide not only resulted in robust weight reduction, but also in clear improvements in assessed cardiometabolic health measures," she added. "For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory."
Lilly is investing in a major phase 3 programme for retatrutide, which it sees as a successor to its fast-growing dual GIP/GLP-1 agonist Zepbound/Mounjaro (tirzepatide) – now the top-selling drug worldwide – and also as a companion to new oral GLP-1 agonist Foundayo (orforglipron) as it battles for market share with main rival Novo Nordisk.
The wager looks likely to be rewarded, as the weight-loss data with retatrutide has so far come in consistently ahead of Zepbound, which has seen its sales rocket after beating Novo Nordisk's injectable GLP-1 agonist Wegovy (semaglutide) in a head-to-head trial.
Analysts at Clarivate have suggested $30 billion-plus revenues are possible with retatrutide, predicting it will become the primary growth driver in the obesity drug market after 2028.
Safety and tolerability will be a factor to watch, and discontinuation rates came in at 4.1% with the 4 mg dose, 6.9% at 9 mg, as 11.3% for the top dose, compared to 4.9% with placebo.
Kenneth Custer, head of cardiometabolic health at Lilly, said that with Zepbound, Foundayo and retatrutide, the company can "match treatments to the needs and preferences of patients…across various stages of their obesity journey."
The company is thought to be waiting for the results of two more trials later this year – TRIUMPH-2 in obesity or overweight and type 2 diabetes, and TRIUMPH-3 in obesity or overweight and established cardiovascular disease – before filing retatrutide for approval in late 2027 or early 2028.
