Lilly reports positive Phase 3 TRANSCEND-T2D-1 results showing retatrutide achieved up to 2.0% A1C reduction and 16.8% weight loss in adults with type 2 diabetes.
Written By: Katherashala Dharan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Eli Lilly and Company has reported positive topline results from the Phase 3 TRANSCEND-T2D-1 clinical trial evaluating retatrutide, an investigational once-weekly triple hormone receptor agonist targeting GIP, GLP-1 and glucagon receptors, in adults with type 2 diabetes.
The randomized, double-blind, placebo-controlled study met its primary and all key secondary endpoints, demonstrating significant reductions in glycated hemoglobin (A1C) and body weight after 40 weeks of treatment when used alongside diet and exercise.
The trial enrolled 537 adults with type 2 diabetes who had inadequate glycemic control with diet and exercise alone and had not received anti-diabetes medications for at least 90 days before enrolment. Participants had a mean baseline A1C of 7.9% and BMI of 35.8 kg/m². Patients were randomized to receive retatrutide 4 mg, 9 mg, 12 mg, or placebo once weekly.
For the primary endpoint, retatrutide achieved substantial improvements in glycemic control. At week 40, participants experienced mean A1C reductions of 1.7%, 2.0%, and 1.9% with the 4 mg, 9 mg and 12 mg doses, respectively, compared with 0.8% with placebo using the efficacy estimand.
Retatrutide also delivered notable weight loss, a key secondary endpoint. Participants receiving the highest dose achieved average weight reductions of up to 16.8% (16.6 kg / 36.6 lbs) from a baseline body weight of 96.9 kg, while placebo-treated patients lost 2.5% on average. Weight reduction continued through the end of the treatment period.
In addition to glycemic and weight improvements, the therapy showed clinically meaningful improvements in cardiometabolic risk markers, including reductions in non-HDL cholesterol, triglycerides and systolic blood pressure.
The safety profile was consistent with other incretin-based therapies. The most common adverse events were gastrointestinal, including nausea, diarrhea and vomiting, primarily occurring during dose escalation. Rates of treatment discontinuation due to adverse events ranged from 2.2% to 5.1% across retatrutide doses, compared with 0% in the placebo group. Mild dysesthesia was reported in a small proportion of treated participants and generally resolved during treatment.
“For many people with type 2 diabetes, achieving both A1C control and meaningful weight loss remains challenging,” said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health. “These results highlight the potential of retatrutide to deliver substantial improvements in both measures.”
Retatrutide is currently being studied in a broad Phase 3 clinical development program investigating its potential across multiple cardiometabolic conditions, including obesity, type 2 diabetes, obstructive sleep apnea, metabolic dysfunction-associated steatotic liver disease, osteoarthritis and cardiovascular outcomes.
Detailed results from TRANSCEND-T2D-1 (NCT06354660) are expected to be presented at the American Diabetes Association Scientific Sessions in June, with additional data from the broader TRANSCEND-T2D program, which has enrolled more than 2,050 participants, anticipated over the coming year.
References
Lilly’s triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes, 19 March 2026, Lilly’s triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes | Eli Lilly and Company
Effect of Retatrutide Compared with Placebo in Adult Participants with Type 2 Diabetes and Inadequate Glycemic Control with Diet and Exercise Alone (TRANSCEND-T2D-1), ClinicalTrials.gov ID NCT06354660, https://clinicaltrials.gov/study/NCT06354660
About the Writer
Katherashala Dharan Kumar, PharmD A dedicated Clinical Researcher with expertise in medical and scientific writing clinical trials, drug safety, and healthcare innovation. Actively contributes to research publications and clinical documentation focused on improving patient outcomes through evidence-based practices and ethical research standards. Believe that every complex data point has a human story waiting to be told. Focusing on providing actionable insights for clinical research.