Phase 3 clinical trial results for retatrutide, a weekly triple-action injection for type 2 diabetes developed by Eli Lilly, were published in The Lancet. The trials demonstrated a reduction in HbA1c and weight compared to a placebo.
The trial included 930 adults with type 2 diabetes who had inadequately controlled blood sugar and a body mass index (BMI) of at least 23. Participants were randomly assigned to receive weekly injections of 4mg, 9mg, or 12mg of retatrutide or a placebo for 40 weeks. After 40 weeks, participants receiving retatrutide experienced an average HbA1c reduction of 1.7 to 1.9 percentage points, while the placebo group saw an average reduction of 0.8 percentage points.
Retatrutide administration also resulted in participants losing an average of 11.5% to 15.3% of their body weight over 40 weeks. In contrast, the placebo group lost an average of 2.6% of their body weight during the same period. The medication's administration was also associated with improvements in cholesterol and blood pressure levels.
Retatrutide mimics the gut hormones GLP-1, GIP, and glucagon to control appetite and blood sugar levels while increasing the body's energy expenditure. Most trial participants reported mild to moderate gastrointestinal symptoms that decreased over time. Fourteen participants experienced serious adverse events during the trial, including two in the placebo group.
Dr. Kath McCullough, special adviser on obesity at the Royal College of Physicians, said, "For many people living with diabetes and obesity, treatments like this could be genuinely life-changing." She added, "However, medications are not a silver bullet. While they are proving to be effective, the long-term goal must be to prevent people from needing them in the first place."
Dr. Marie Spreckley, a specialist in diabetes prevention at IMS Epidemiology, University of Cambridge, said, "The magnitude of weight loss observed is particularly notable. However, because this study compared retatrutide with placebo rather than semaglutide or tirzepatide, it is not possible to determine from this data whether retatrutide is superior, equivalent or inferior to currently available therapies." She added, "Direct head-to-head trials will be required before firm conclusions can be drawn regarding comparative effectiveness." Spreckley also stated, "Patients need support to maintain adequate nutritional intake, preserve muscle mass and maximise long-term health during treatment."
Dr. Lucy Chambers, head of research impact and communications at Diabetes UK, said, "These encouraging findings show that this new class of drug for type 2 diabetes could deliver dual benefits for both weight loss and blood-sugar management." Chambers added, "We look forward to further research to understand its long-term effects and how it compares to treatments already available on the NHS."