Lilly's triple agonist retatrutide passes diabetes test

Eli Lilly has positive phase 3 results for its triple agonist retatrutide in type 2 diabetes (T2D) to go with its earlier encouraging data as a weight-loss therapy.

The GIP, GLP-1 and glucagon agonist met its objectives in the TRANSCEND-T2D-1 by delivering significant improvements in blood glucose control, measured using the haemoglobin A1c biomarker, as well as an average weight loss of 16.8% over 40 weeks of follow-up.

The result builds on the results of the TRIUMPH-4 study in people living with overweight or obesity and knee osteoarthritis, using a higher dose of retatrutide, which delivered weight reductions of nearly 29% at 68 weeks.

Lilly views the next-generation drug as a key component of its plan to ramp up market share in the diabetes and weight-loss category, building on its current strong position with dual GIP/GLP-1 drug tirzepatide, which is marketed as Mounjaro for diabetes and Zepbound for obesity and brought in global sales of $36 billion last year.

Analysts at Clarivate suggest similar $30 billion-plus revenues are possible with retatrutide, thanks to a mechanism that combines reducing calorie intake and augmenting energy expenditure, predicting it will become the primary growth driver in the obesity drug market after 2028.

Drilling into the TRANSCEND-T2D-1 data, once-weekly injections of retatrutide reduced A1c levels between 1.7% and 2.0%, depending on the dose, with weight loss as a percentage of starting body weight ranging between 11.5% and 16.8%. Lilly has also reported "clinically meaningful" improvements from baseline across various cardiovascular risk factors, including blood cholesterol, triglycerides, and systolic blood pressure.

The weight loss showed no signs of plateauing at the 40-week timepoint, said the company, and retatrutide's safety was in line with earlier studies and other incretin-based therapies, with mainly gastrointestinal side effects like nausea, diarrhoea, and vomiting. Treatment discontinuation rates were also fairly low, at around 5% for the top dose (12 mg).

Lilly's head of cardiometabolic health, Kenneth Custer, said that many people with T2D struggle to achieve improved glucose control and weight loss.

"With triple agonist retatrutide, we set out to make a molecule that could help patients achieve substantial A1C reduction and weight loss," he added. "These results support the remarkable potential of this novel molecule for people living with type 2 diabetes."

Retatrutide is just one part of Lilly's plan to expand its diabetes and weight-loss franchise, as the company is currently waiting for an FDA decision on its oral GLP-1 agonist orforglipron, playing catch-up with Novo Nordisk's already approved Wegovy (semaglutide) pill. The company has said it is hoping to file the triple agonist for weight loss this year and T2D in 2027.