TRANSCEND-T2D-1: Retatrutide Demonstrates Superior Weight Loss and A1c Results Versus Placebo

Eli Lilly’s investigative triple agonist retatrutide has displayed substantial results in A1c reduction and weight loss among patients with type 2 diabetes (T2D), according to data from the phase 3 TRANSCEND-T2D-1 trial.¹

Presented at the American Diabetes Association (ADA) Scientific Sessions 2026 in New Orleans, Louisiana, by Harpreet Singh Bajaj, MD, MPH, a clinical endocrinologist at LMC Diabetes & Endocrinology and chief medical officer of the Canadian Diabetes Prevention Program, these data reflect the GLP-1/GIP/glucagon triple agonist’s first phase 3 trial in this patient population.¹

“Obesity drives more than 200 downstream diseases, yet we have historically treated those conditions one at a time and in silos,” Ania Jastreboff, MD, PhD, professor of medicine and pediatrics at the Yale School of Medicine and the director of the Yale Obesity Research Center, said in a statement. “These findings demonstrate what may be possible when we treat obesity and impact overall health, and what this could mean for people living with obesity and its related complications.”¹

TRANSCEND-T2D-1 is a phase 3, randomized, double-blind, placebo-controlled study investigating the efficacy and safety of retatrutide with placebo in adults with T2D inadequately controlled with diet and exercise alone. The study’s primary outcome was to demonstrate retatrutide’s superiority to placebo in A1c reduction from baseline after 40 weeks.¹

Eligible participants were required to have A1c between ≥7% and ≤9.5% and a body mass index (BMI) ≥23 kg/m2 at visit 1, as well as having not taken anti-diabetes medication for ≥90 days prior to visit 1. A total of 537 patients were ultimately enrolled and randomly assigned in a 1:1:1:1 ratio to either retatrutide 4 mg, 9 mg, or 12 mg, or placebo. Those randomized to receive retatrutide began treatment with 2 mg once weekly and increased the dose in a stepwise approach every 4 weeks until reaching the target dose.²

Ultimately, patients receiving retatrutide reached an average A1c reduction of ≤2.0% from a baseline of 7.9% - additionally, 90% of all participants on retatrutide achieved an A1c below 7%, the ADA’s general target for T2D, and ≤85% achieved ≤6.5%. Patients receiving retatrutide 12 mg lost an average of 36.6 lbs with no sign of plateauing by 40 weeks. Retatrutide also showed reductions of ≤39.6% in triglycerides, 19.8% in non-HDL cholesterol, 6.4 mmHg in systolic blood pressure, and 4.9 inches in waist circumference by 40 weeks.¹

The most common adverse events with retatrutide 4 mg, 9 mg, 12 mg, and placebo (respectively) were nausea (16.4%, 19.5%, 26.5% vs 3.7%), diarrhea (18.7%, 26.3%, 22.8% vs 4.5%), and vomiting (15.7%, 15%, 17.6% vs 2.2%). Dysesthesia (4.5%, 2.3%, 4.4% vs 0%) and urinary tract infections (0.7%, 1.5%, 2.9% vs 0%) were also noted, but results were generally mild to moderate and most resolved during treatment. Discontinuation rates due to adverse events were 2.2%, 4.5%, and 5.1% with retatrutide, respectively, compared with 0% among placebo recipients.¹

“Of course, long-term outcomes - the question of whether this molecule, similarly to GLP-1s, will show long-term cardiovascular benefits, kidney benefits, or liver outcome benefits - is still unknown at this time,” Bajaj said in a press briefing at ADA 2026. “That’s a question that I think is very clinically relevant and very interesting, and I think that with patients, we will generate that data as well.”

References

1. Bajaj H, Welch M, Shah P, et al. Results of First Phase 3 Study of Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist in Patients with T2D (TRANSCEND-T2D-1). Abstract presented at the American Diabetes Association (ADA) Scientific Sessions 2026, New Orleans, LA. June 5-8, 2026.

2. Eli Lilly. Lilly’s triple agonist, retatrutide, demonstrated significant reductions in A1c and weight in first Phase 3 trial for treatment of type 2 diabetes. March 19, 2026. Accessed June 6, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-demonstrated-significant