Lilly fleshes out triple G data in diabetes and obesity
Eli Lilly's triple G agonist retatrutide has achieved impressive weight loss in patients with type 2 diabetes and obesity, boosting its credentials as the next big thing in cardiometabolic diseases.
The readout from the TRIUMPH-2 study at the European Association for the Study of Diabetes (EASD) congress in Milan, Italy, showed that patients treated with a 12 mg weekly retatrutide injection lost an average of 20.8% of their body weight over 80 weeks, with more than half falling under the threshold for obesity by that time.
Lilly had teased the results of the 2,025-patient trial earlier this year and presented the full dataset at EASD as the data was published in The Lancet. Two lower doses of the GIP, GLP-1, and glucagon agonist – 4 mg and 8 mg – achieved weight loss of 12.7% and 19.1%, respectively, with a 4% decline in the placebo group.
Reductions in HbA1c, a marker of glucose control, fell by an average of 1.5% across all three retatrutide dosage groups, compared to a 0.2% reduction with placebo, with 40% of those on the triple G drug achieving a level of 5.7% or less – which is considered a normal blood sugar level.
The improvements in weight and blood glucose were accompanied by reductions in cardiovascular risk factors, including non-HDL cholesterol, triglycerides, blood pressure, and high-sensitivity C-reactive protein (hsCRP), with a side-effect profile and discontinuation rates that look comparable to other incretin-directed weight-loss therapies.
Moreover, the activity across all dose levels sets up retatrutide as a more-potent successor to Lilly's blockbuster dual GIP/GLP-1 agonist Mounjaro/Zepbound (tirzepatide), now leading the market since overtaking Novo's rival GLP-1 agonist products Ozempic/Wegovy (semaglutide).
Earlier this year, Lilly previously reported similarly strong results with retatrutide in the TRIUMPH-1 study in non-diabetic people with obesity, which revealed dramatic weight loss of up to 28.3% at 80 weeks, which the company said compared with the level expected after bariatric surgery.
"With efficacy this powerful and consistent across our phase 3 programme, we believe retatrutide could become an important option for people living with type 2 diabetes and obesity," said Kenneth Custer, Lilly's head of cardiometabolic health.
Armed with the new data, Lilly will press ahead with plans to file for approval of retatrutide in the first quarter of 2027, and is also awaiting data from TRIUMPH-2 from a cohort of patients with sleep apnoea, which should be available soon and could add another facet to the marketing application.
New Zepbound, Foundayo data at EASD
Lilly also presented new trial results with Zepbound and its oral HLP-1 agonist Foundayo (orforglipron) at EADV, claiming advantages over rival Novo products – albeit in indirect comparisons.
A new analysis of data from the SURMOUNT-1 and STEP UP trials of Zepbound suggests that Zepbound is more effective at achieving weight loss in people living with obesity compared to Novo's new high-strength Wegovy HD formulation – with a 4.5% difference between the two drugs at 72 weeks – while three times as many patients achieved at least a 20% body weight reduction.
Meanwhile, Lilly highlighted a comparison of Foundayo with Novo's Wegovy pill, drawing on data from the ACHIEVE-3 and PIONEER PLUS studies, which it said showed 1.5% greater weight loss and 0.3% greater A1C reduction after a year.
