Eli Lilly’s investigational first-in-class GIP, glucagon-like peptide 1 receptor (GLP-1R) and glucagon triple hormone receptor agonist has met its primary endpoints in a Phase III trial.
In the TRANSCEND-T2D-1 study (NCT06297603), retatrutide led to an A1C reduction of between 1.7% and 2.0% after 40 weeks in patients with type 2 diabetes (T2D) with inadequate glycemic control with diet and exercise alone. This was compared to 0.8% with a placebo.
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A key secondary endpoint was weight loss, with patients taking retatrutide losing up to an average of 36.6lb, or 16.8%, using the efficacy estimate. Weight loss continued through the end of the treatment period.
Retatrutide also showed clinically meaningful improvements from baseline across key cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure.
Lilly executive vice-president and cardiometabolic health president Dr Kenneth Custer said: “For many people with T2D, it is a struggle to achieve both A1C control and weight loss, since obesity has historically been harder to treat for those with T2D.
“With triple agonist retatrutide, we set out to make a molecule that could help patients achieve substantial A1C reduction and weight loss. These results support the remarkable potential of this novel molecule for people living with T2D, with up to 2% A1C improvement and a nearly 17% weight loss in 40 weeks of treatment.”
Adverse events (AEs) were consistent with other incretin-based therapies, with the most common events being nausea, diarrhoea and vomiting.
Detailed TRANSCEND-T2D-1 results will be presented at the American Diabetes Association (ADA) Scientific Sessions in June 2026 and published in a peer-reviewed journal.
A1C reduction with retatrutide was not as significant as that seen with Lilly’s first weight loss drug Mounjaro (tirzepatide), which touted drops of 1.7% to 2.4% after 40 weeks.
Retatrutide also met its endpoints in a Phase III weight loss trial, lowering weight by up to an average of 28.7% and reducing knee osteoarthritis pain.
There are another six readouts expected for retatrutide over the next few months, which include a maintenance dose of 4mg, in addition to 9mg and 12mg doses.
GlobalData, parent company of Clinical Trials Arena, predicts a 2027 approval for retatrutide, with a 2031 sales forecast of $15.6bn in 2031, according to the patient-based forecast.
Lilly’s flagship weight loss drug, Zepbound (tirzepatide), generated sales of $3.6bn in Q3 2025 alone. The company is also awaiting a decision from the US Food and Drug Administration (FDA) on the approval of its oral GLP-1RA orforglipron, which has succeeded in Phase III trials in both obesity and T2D.
Lilly’s main rival, Novo Nordisk, has already gained approval for its oral GLP-1RA Wegovy (semaglutide) after a successful Phase III trial. The drug is available on the US market.
GlobalData predicts that the obesity market will reach $206.5bn, up from $12.3bn across the 68 markets, with $981.3m of that expected from the Asia-Pacific region.
