Eli Lilly's triple hormone drug retatrutide delivers 16.8% weight loss in phase 3 trial

Eli Lilly on Thursday said its next weight loss drug retatrutide, which targets three hormones instead of the usual one or two, delivered nearly 17% weight loss in patients with type 2 diabetes over 40 weeks in its first Phase 3 trial. Participants continued losing weight through the entire treatment period with no plateau observed, a result the company said sets it apart from existing drugs in the class.

Retatrutide is a once-weekly injectable that works on three hormones simultaneously, GIP, GLP-1 and glucagon, which together regulate blood sugar, appetite and fat metabolism. Current weight loss drugs like semaglutide and tirzepatide work on one or two of these hormones. Retatrutide targets all three, which is why Lilly calls it a triple agonist and believes it could deliver stronger results for patients who struggle to control both blood sugar and weight.

In the TRANSCEND-T2D-1 trial, which enrolled 537 adults with type 2 diabetes, participants taking the highest dose of retatrutide at 12 mg lost an average of 36.6 lbs, or 16.8% of their body weight, over 40 weeks. Blood sugar levels, measured by HbA1c, fell by an average of 2.0% from a baseline of 7.9%. The drug also showed improvements in cardiovascular risk factors including non-HDL cholesterol, triglycerides and systolic blood pressure.

"For many people with type 2 diabetes, it is a struggle to achieve both A1C control and weight loss, since obesity has historically been harder to treat for those with type 2 diabetes," said Kenneth Custer, executive vice president and president, Lilly Cardiometabolic Health. "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 type 2 diabetes, with up to 2% A1C improvement and nearly 17% weight loss in 40 weeks of treatment."

The most common side effects were nausea, diarrhoea and vomiting, mainly during the early weeks of treatment, consistent with other drugs in the class.

The TRANSCEND-T2D Phase 3 programme spans three global trials and has enrolled more than 2,050 participants. Full results from TRANSCEND-T2D-1 will be presented at the American Diabetes Association Scientific Sessions in June and published in a peer-reviewed journal. Additional trial results are expected over the next year.

Retatrutide is currently investigational and not yet approved by any regulatory authority. Lilly is studying the drug across multiple conditions including obesity, knee osteoarthritis, sleep apnea, chronic lower back pain and cardiovascular and renal outcomes. The drug is still years away from regulatory approval, but if cleared, it would eventually be relevant for markets like India, which is home to close to 9 crore adults with type 2 diabetes, according to the International Diabetes Federation.

According to Eli Lilly's full year 2025 results, Mounjaro and Zepbound together posted combined sales of $36.5 billion, accounting for 56% of the company's total revenues of $65.2 billion, making tirzepatide the world's best-selling drug in 2025.

According to Goldman Sachs Research, the global anti-obesity drug market is projected to reach $95 billion by 2030.