Retatrutide shows substantial weight loss, glycemic control in obesity and type 2 diabetes | ADA 2026

Phase 3 trial data presented Saturday at the American Diabetes Association (ADA) 2026 Scientific Sessions in New Orleans showed that retatrutide produced substantial reductions in body weight and A1C across two distinct patient populations: adults with type 2 diabetes (T2D) and adults with obesity or overweight. Eli Lilly's investigational glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon triple receptor agonist also showed a safety profile consistent with existing GLP-1 receptor agonists.

The findings from TRANSCEND-T2D-1 and TRIUMPH-1 represent the first phase 3 data for retatrutide, with TRANSCEND-T2D-1 data simultaneously published in The Lancet.

TRANSCEND-T2D-1: Weight loss and glycemic control in early-stage T2D

TRANSCEND-T2D-1 enrolled 537 adults with recent-onset type 2 diabetes with a mean disease duration of 2.5 years who had inadequate glycemic control on diet and exercise alone. Baseline A1C was between 7.0% and 9.5% and BMI was at least 23 kg/m². Participants were randomized 1:1:1:1 to receive once-weekly injections of retatrutide at 4 mg, 9 mg, or 12 mg, or placebo over 40 weeks.

Patients receiving retatrutide achieved a mean A1C reduction of up to 2.0% from a baseline of 7.9%. Ninety percent of participants on retatrutide reached the ADA's general A1C target of below 7%, and up to 85% achieved 6.5% or lower. Those on the 12 mg dose lost an average of 36.6 pounds — a 16.8% reduction — with no sign of plateauing at week 40. The drug also reduced triglycerides by up to 39.6%, non-HDL cholesterol by 19.8%, systolic blood pressure by 6.4 mmHg, and waist circumference by 4.9 inches.

“It is well established that weight reduction with currently available medications is often less for people living with type 2 diabetes compared to those without diabetes. As no other trial has reported this magnitude of weight loss, this novel treatment, retatrutide, has the potential to meaningfully improve the lives of newly diagnosed individuals with type 2 diabetes through life-changing weight and blood glucose management,” Harpreet Singh Bajaj, MD, MPH, lead author of the study, said in a statement. “The magnitude of weight loss observed with retatrutide has the potential to slow disease progression and reshape how we treat and manage type 2 diabetes.”

Adverse events were consistent with the GLP-1 class. The most common were nausea, diarrhea, and vomiting, which were generally mild to moderate and resolved during treatment. Discontinuation rates ranged from 2.2% to 5.1% across the active arms versus 0% in the placebo group.

TRIUMPH-1: Bariatric-level weight loss in obesity

TRIUMPH-1 was larger in scope, enrolling 2,339 adults with obesity (BMI of 30 kg/m² or higher) or overweight with at least one weight-related comorbidity. The 80-week, placebo-controlled trial also included two nested basket trials evaluating retatrutide's effects in patients with knee osteoarthritis and moderate-to-severe obstructive sleep apnea.

Participants on retatrutide 9 mg and 12 mg lost an average of 64.4 pounds (25.9%) and 70.3 pounds (28.3%), respectively, at week 80. The 4 mg dose, which required only a single dose escalation step, produced an average loss of 47.2 pounds (19.0%). Among participants with a baseline BMI of at least 35, the 12 mg dose drove an average loss of 85 pounds — a 30.3% reduction. Sixty-five percent of those on the 12 mg dose reached a BMI below 30, and 33.3% fell below the overweight threshold of 25.

Beyond weight, retatrutide produced a 73.1% reduction in Western Ontario and McMaster Universities Osteoarthritis Index knee pain scores in the osteoarthritis basket trial and a 60.6% reduction in apnea-hypopnea index events in the sleep apnea basket trial — outcomes that investigators characterized as clinically meaningful.

“Importantly, in addition to significant weight reduction, treatment with retatrutide resulted in improvements in health outcomes — from decreased knee pain to fewer sleep disturbances, to clear improvements in cardiometabolic measures; effectively treating obesity meaningfully impacts the overall health of people living with obesity,” lead investigator Ania M. Jastreboff, MD, PhD, director of the Yale Obesity Research Center, said in a statement.

Additional phase 3 trials are underway comparing retatrutide against semaglutide in T2D (TRANSCEND-T2D-2), evaluating it in combination with insulin in patients with chronic kidney disease (TRANSCEND-T2D-3), and assessing its effects in patients with obesity and cardiovascular disease (TRIUMPH-3).

"Across TRIUMPH-1 and TRANSCEND-T2D-1, retatrutide delivered substantial weight loss, meaningful A1C reduction, and improvements in knee osteoarthritis pain and moderate-to-severe obstructive sleep apnea, a breadth and magnitude of outcomes that's striking to see with a single therapy," Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health, said in a press release. "By addressing weight, glycemia and obesity-related complications together, these results highlight retatrutide's potential across the cardiometabolic spectrum and reinforce our commitment to delivering options that meet patients' needs and preferences."