For the primary endpoint, retatrutide lowered A1C by an average of 1.7% to 2.0% across doses at 40 weeks in TRANSCEND-T2D-1

Participants taking retatrutide 12 mg lost an average of 36.6 lbs (16.8%)

No weight loss plateau was observed with retatrutide, with participants continuing their weight loss trajectory through 40 weeks

Eli Lilly and Company announced positive topline results from TRANSCEND-T2D-1, a Phase 3 clinical trial evaluating the efficacy and safety of retatrutide, an investigational first-in-class GIP, GLP-1and glucagon triple hormone receptor agonist, as an adjunct to diet and exercise. The trial enrolled adults diagnosed with type 2 diabetes with inadequate glycemic control with diet and exercise alone, and a mean duration of diabetes of 2.5 years. In the study, retatrutide met the primary and all key secondary endpoints, delivering superior A1C reduction and weight loss at 40 weeks compared to placebo, using both the efficacy and treatment-regimen estimands.^1,2 For the primary endpoint, participants taking retatrutide achieved average A1C reductions of up to 2.0%, using the efficacy estimand. For a key secondary endpoint, participants taking retatrutide lost up to an average of 36.6 lbs (16.8%), using the efficacy estimand. Weight loss continued through the end of the treatment period.

"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, Ph.D., 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."

TRANSCEND-T2D-1 Efficacy Results

Retatrutide also showed clinically meaningful improvements from baseline across key cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure.³

Consistent with the types of adverse events seen in clinical trials for other incretin-based therapies, the most common adverse events among participants treated with retatrutide (4 mg, 9 mg, 12 mg) were nausea (16.4%, 19.5%, 26.5%, respectively vs. 3.7% with placebo), diarrhea (18.7%, 26.3%, 22.8%, respectively vs. 4.5% with placebo) and vomiting (15.7%, 15.0%, 17.6%, respectively vs. 2.2% with placebo), and occurred primarily during dose escalation. Incidence of dysesthesia occurred in 4.5%, 2.3% and 4.4% (4 mg, 9 mg and 12 mg, respectively) of patients treated with retatrutide, compared to 0.0% with placebo. These dysesthesia events were generally mild, with a majority resolving during treatment. Discontinuation rates due to adverse events were 2.2%, 4.5% and 5.1% with retatrutide 4 mg, 9 mg and 12 mg, respectively, compared to 0.0% with placebo.

Detailed TRANSCEND-T2D-1 results will be presented at the American Diabetes Association Scientific Sessions in June and published in a peer-reviewed journal. Additional results from the retatrutide clinical trial program are expected over the next year.