Eli Lilly and Company has reported positive topline results from TRANSCEND-T2D-1, a Phase 3 clinical trial of retatrutide, an investigational triple agonist targeting GIP, GLP-1 and glucagon receptors, in adults with type 2 diabetes. The study evaluated retatrutide as an adjunct to diet and exercise in participants with inadequate glycemic control and a mean diabetes duration of 2.5 years. In the trial, retatrutide met the primary and all key secondary endpoints, showing superior reductions in A1C and body weight at 40 weeks compared with placebo, based on both efficacy and treatment-regimen estimands.
For the primary endpoint, participants treated with retatrutide achieved average A1C reductions of up to 2.0%, using the efficacy estimand. For a key secondary endpoint, participants receiving retatrutide lost up to an average of 36.6 pounds, corresponding to 16.8% weight loss, also using the efficacy estimand. Weight loss continued through the end of the 40-week treatment period. The company highlighted the potential of the triple-agonist approach to address both glycemic control and obesity in people with type 2 diabetes.
Retatrutide treatment was also associated with clinically meaningful improvements from baseline in several cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure. The most common adverse events in the 4 mg, 9 mg and 12 mg retatrutide groups were gastrointestinal in nature, consistent with other incretin-based therapies. Reported rates of nausea were 16.4%, 19.5% and 26.5% for the three doses, respectively, compared with 3.7% for placebo; diarrhea occurred in 18.7%, 26.3% and 22.8% of patients, compared with 4.5% for placebo; and vomiting occurred in 15.7%, 15.0% and 17.6% of patients, compared with 2.2% for placebo. These events occurred primarily during dose escalation.
Dysesthesia was reported in 4.5%, 2.3% and 4.4% of participants in the 4 mg, 9 mg and 12 mg retatrutide groups, respectively, and was not reported in the placebo group. According to Lilly, these dysesthesia events were generally mild, with most resolving during treatment. Discontinuation rates due to adverse events were 2.2%, 4.5% and 5.1% for the 4 mg, 9 mg and 12 mg retatrutide arms, respectively, compared with 0.0% for placebo.
Lilly said detailed results from TRANSCEND-T2D-1 will be presented at the American Diabetes Association Scientific Sessions in June and submitted for publication in a peer-reviewed journal. Additional data from the broader retatrutide clinical development program are expected over the next year.
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