In TRIUMPH-1, participants on retatrutide 12 mg lost an average of 70.3 lbs (28.3%) over 80 weeks, with 65.3% achieving a BMI below 30, no longer meeting the BMI criteria for obesity

In addition to weight loss, retatrutide reduced knee osteoarthritis pain by up to 4.3 points (73.1%) and moderate-to-severe obstructive sleep apnea severity by up to 36.1 events per hour (60.6%)

In TRANSCEND-T2D-1, participants on retatrutide achieved A1C reductions of up to 2.0% and weight loss of up to 36.6 lbs (16.8%) at 40 weeks, with up to 46% achieving a normal A1C

 Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), announced additional positive results from pivotal Phase 3 trials of retatrutide, an investigational, first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist, showing substantial weight loss along with meaningful improvements across knee osteoarthritis pain, moderate-to-severe obstructive sleep apnea, and type 2 diabetes – common obesity-related conditions.^1,2 The findings from TRIUMPH-1 and TRANSCEND-T2D-1 were presented at the American Diabetes Association (ADA) 86th Scientific Sessions, with TRANSCEND-T2D-1 results simultaneously published in The Lancet.

"Obesity drives more than 200 downstream diseases, yet we have historically treated those conditions one at a time and in silos," said Ania Jastreboff, M.D., Ph.D., Professor of Medicine & Pediatrics (Endocrinology) at the Yale School of Medicine, Director of the Yale Obesity Research Center (Y-Weight), and lead investigator. "In TRIUMPH-1 and TRANSCEND-T2D-1, treatment with retatrutide resulted in substantial weight reduction together with clinically meaningful improvements in glycemia, knee osteoarthritis pain, and obstructive sleep apnea, with many individuals reaching what are classified as healthy-range weight and normal blood sugar levels. 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."

TRIUMPH-1 included an overarching trial for adults with obesity and two nested basket trials: one for knee osteoarthritis pain and one for moderate-to-severe obstructive sleep apnea. Retatrutide met the primary endpoints in each trial at 80 weeks, delivering powerful weight loss along with significant improvements in knee osteoarthritis pain and obstructive sleep apnea. Participants on retatrutide 9 mg and 12 mg lost an average of 64.4 lbs (25.9%) and 70.3 lbs (28.3%), respectively, while those on the 4 mg dose, reached with a single dose escalation step, lost an average of 47.2 lbs (19.0%).³ Notably, 65.3% of participants on retatrutide 12 mg achieved a BMI <30, and 33.3% reached a BMI <25, representing healthy BMI. In a pre-specified extension for participants with baseline BMI ≥35, those continuing on retatrutide 12 mg through 104 weeks lost an average of 85.0 lbs (30.3%). In addition to improving weight measures, retatrutide reduced Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores by up to 4.3 points (73.1%) from a baseline of 6.0 in participants with knee osteoarthritis and apnea-hypopnea index (AHI) by up to 36.1 events per hour (60.6%) from a baseline of 58.6 events per hour in participants with moderate-to-severe obstructive sleep apnea.⁴

"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," said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. "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."

In TRANSCEND-T2D-1, retatrutide met the primary and all key secondary endpoints at 40 weeks in adults with type 2 diabetes, delivering significant A1C reduction along with substantial weight loss. For the primary endpoint, participants taking retatrutide achieved average A1C reductions of up to 2.0% from a baseline of 7.9%. Notably, up to 90% of participants taking retatrutide achieved an A1C below 7.0%, the American Diabetes Association's general target for type 2 diabetes, and up to 85% achieved 6.5% or below, a more stringent goal that may be right for adults earlier in their disease journey.⁵ In addition, up to 46% of participants achieved an A1C below 5.7%, the threshold for normoglycemia. Individuals taking retatrutide 12 mg also lost an average of 36.6 lbs (16.8%), with weight loss not yet plateauing at 40 weeks.

Across both trials, retatrutide also showed significant improvements from baseline across certain cardiovascular risk factors. In TRIUMPH-1, retatrutide delivered reductions of up to 41.0% in triglycerides, 24.2% in non-HDL cholesterol, 12.3 mmHg in systolic blood pressure, and 9.5 in (24.1 cm) in waist circumference at 80 weeks. In TRANSCEND-T2D-1, retatrutide demonstrated reductions of up to 39.6% in triglycerides, 19.8% in non-HDL cholesterol, 6.4 mmHg in systolic blood pressure, and 4.9 in (12.4 cm) in waist circumference at 40 weeks.⁶

The types of adverse events seen in TRIUMPH-1 and TRANSCEND-T2D-1 were generally consistent with trials of other incretin-based therapies. In TRIUMPH-1, the most common adverse events with retatrutide (4 mg, 9 mg, 12 mg vs. placebo, respectively) were nausea (28.6%, 38.4%, 42.4% vs. 14.8%), diarrhea (25.2%, 34.1%, 32.0% vs. 13.5%), constipation (23.8%, 25.9%, 26.1% vs. 10.9%), vomiting (10.6%, 22.8%, 25.3% vs. 4.8%), and upper respiratory tract infection (14.2%, 12.2%, 13.1% vs. 11.6%). Incidences of dysesthesia (5.1%, 12.3%, 12.5% vs. 0.9%) and urinary tract infections (7.5%, 8.8%, 8.4% vs. 5.3%) were also observed; these events were generally mild to moderate, the majority resolved during treatment, and most participants continued taking retatrutide. Discontinuation rates due to adverse events were 4.1%, 6.9%, and 11.3% with retatrutide, respectively, compared with 4.9% with placebo.

In TRANSCEND-T2D-1, the most common adverse events with retatrutide (4 mg, 9 mg, 12 mg vs. 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%, 15.0%, 17.6% vs. 2.2%). Incidences of dysesthesia (4.5%, 2.3%, 4.4% vs. 0.0%) and urinary tract infections (0.7%, 1.5%, 2.9% vs. 0.0%) were also observed; these events were generally mild to moderate, the majority resolved during treatment, and most participants continued taking retatrutide. Discontinuation rates due to adverse events were 2.2%, 4.5%, and 5.1% with retatrutide, respectively, compared with 0.0% with placebo.