In TRIUMPH-2, participants with obesity and type 2 diabetes taking retatrutide 12 mg lost an average of 49.6 lbs (20.8%) over 80 weeks, with more than half no longer meeting the BMI criteria for obesity
Participants with a baseline BMI of 35 or higher who took retatrutide 12 mg lost up to an average of 60.8 lbs (23.4%) of their body weight
Retatrutide reduced A1C by up to an average of 1.6%, with up to 40.0% reaching an A1C of 5.7%
INDIANAPOLIS, Sept. 29, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), today announced detailed results from TRIUMPH-2, a Phase 3 trial evaluating the efficacy and safety of retatrutide, an investigational, first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist, in adults with type 2 diabetes and obesity or overweight. At 80 weeks, all doses of retatrutide (4 mg, 9 mg, and 12 mg) delivered substantial weight loss and reductions in A1C.1 Results were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, and simultaneously published in The Lancet.
"The vast majority of people with type 2 diabetes are also living with obesity, and treating the two together has always been a challenge," said Juan P. Frías, M.D., Medical Director and Principal Investigator, Los Angeles Institute for Metabolic Research. "In TRIUMPH-2, retatrutide reduced both weight and blood sugar substantially, with more than half of participants no longer qualifying as having obesity and up to 40% reaching an A1C in the normal range. Results such as these may change what we set out to achieve with a single therapy for adults living with type 2 diabetes and obesity."
Participants taking retatrutide 4 mg, 9 mg, and 12 mg lost an average of 29.8 lbs (12.7%), 45.4 lbs (19.1%), and 49.6 lbs (20.8%), respectively. Among participants with a baseline BMI of 35 or higher, those taking retatrutide 12 mg lost an average of 60.8 lbs (23.4%). By the end of the study, 59.5% of participants taking retatrutide 12 mg no longer met the BMI criteria for obesity.
Beyond substantially reducing weight, retatrutide also helped participants better control their A1C. Participants taking retatrutide 9 mg and 12 mg reduced their A1C by an average of 1.6% and 1.5%, respectively, while those taking 4 mg reduced their A1C by an average of 1.4%. Notably, up to 40.0% of participants reached an A1C of 5.7%, which is considered a normal blood sugar level.
Retatrutide also meaningfully reduced certain cardiovascular risk factors, with the highest dose delivering average reductions of 39.5% in triglycerides, 19.6% in non-HDL cholesterol, 10.8 mmHg in systolic blood pressure, 6.7 in (16.9 cm) in waist circumference, and 58.3% in high-sensitivity C-reactive protein (hsCRP).
"TRIUMPH-2 shows what the next generation of cardiometabolic medicine could deliver: substantial weight loss, A1C reduction and improvements across other critical cardiovascular risk factors," said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. "With efficacy this powerful and consistent across our Phase 3 program, we believe retatrutide could become an important option for people living with type 2 diabetes and obesity."
In TRIUMPH-2, the most common adverse events with retatrutide (4 mg, 9 mg, 12 mg vs. placebo, respectively) were diarrhea (27.4%, 33.5%, 33.6% vs. 13.2%), nausea (13.7%, 20.8%, 28.0% vs. 8.0%), constipation (14.0%, 16.2%, 16.8% vs. 9.4%), decreased appetite (5.8%, 12.3%, 17.1% vs. 4.5%), and vomiting (5.5%, 10.2%, 15.7% vs. 4.2%). Incidences of dysesthesia and urinary tract infections were 4.5%, 5.6%, 7.3% vs. 0.7% and 3.8%, 6.3%, 8.0% vs. 6.6% with retatrutide 4 mg, 9 mg, 12 mg vs. placebo, respectively. These events were generally mild to moderate, and the majority resolved during treatment. Discontinuation rates due to adverse events in TRIUMPH-2 were 3.8% (4 mg), 11.6% (9 mg), and 7.7% (12 mg) with retatrutide, compared with 4.9% for placebo.
Lilly plans to submit a Biologics License Application (BLA) in Q1 2027 to the U.S. Food and Drug Administration. Additional results from the obstructive sleep apnea trial within TRIUMPH-2 will be presented at a future medical meeting and published in a peer-reviewed journal.
About retatrutide
Retatrutide is an investigational, once-weekly, triple hormone receptor agonist. Retatrutide is a single molecule that activates the body's receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon. Lilly is studying retatrutide in several Phase 3 clinical trials to evaluate its potential efficacy and safety in obesity and overweight with at least one weight-related medical problem, type 2 diabetes, knee osteoarthritis pain, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease. Retatrutide is an investigational molecule that cannot be legally sold or marketed for human use.
About TRIUMPH-2 and the TRIUMPH clinical trial program
TRIUMPH-2 (NCT05929079) is a Phase 3, 80-week, randomized, double-blind and placebo-controlled trial under a basket design investigating the efficacy and safety of retatrutide once weekly compared with placebo in participants with type 2 diabetes and obesity or overweight. TRIUMPH-2 included a master trial for obesity and type 2 diabetes and a basket trial for moderate-to-severe obstructive sleep apnea. The study randomized 1,152 participants in a 1:1:1:1 ratio to receive retatrutide 4 mg, 9 mg, 12 mg, or placebo. Participants randomized to retatrutide initiated treatment with 2 mg once weekly and increased the dose in a stepwise approach every four weeks until reaching the target dose of 4 mg (via a step at 2 mg), 9 mg (via steps at 2 mg, 4 mg, and 6 mg) or 12 mg (via steps at 2 mg, 4 mg, 6 mg, and 9 mg). TRIUMPH-2 included a post-treatment follow-up period of 4 weeks.
The initial TRIUMPH Phase 3 clinical development program is evaluating the safety and efficacy of retatrutide for the treatment of patients with obesity or overweight, type 2 diabetes, moderate-to-severe obstructive sleep apnea (OSA) and obesity and knee osteoarthritis pain across four global registrational trials. The program, which began in 2023, has enrolled more than 5,800 participants with additional results anticipated over the next year.
Endnotes
- All data in this press release represent the efficacy estimand.
- The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and modifications) for 80 weeks without initiating prohibited weight management treatments (and glycemic rescue therapy for glycemic endpoints only).
U.S. FOUNDAYO INDICATION AND SAFETY SUMMARY WITH WARNINGS
Foundayo (fown-DAY-oh) is a prescription medicine used with a reduced-calorie diet and increased physical activity to help adults with obesity, or some adults with overweight who also have weight-related medical problems, to lose excess body weight and keep the weight off.
- Foundayo should not be used with other GLP-1 receptor agonist medicines.
- It is not known if Foundayo is safe and effective for use in children.
Warnings – Foundayo may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider.
- Do not use Foundayo if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).
- Do not use Foundayo if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Do not use Foundayo if you have had a serious allergic reaction to orforglipron or any of the ingredients in Foundayo.
Foundayo may cause serious side effects, including:
Inflammation of the pancreas (pancreatitis). Stop taking Foundayo and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without nausea or vomiting. Sometimes you may feel the pain from your abdomen to your back.
Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Foundayo. Tell your healthcare provider if you have stomach problems that are severe or will not go away.
Dehydration leading to kidney problems. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.
Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Foundayo with medicines that can cause low blood sugar, such as an insulin or sulfonylurea. Signs and symptoms of low blood sugar may include dizziness or light-headedness, sweating, confusion or drowsiness, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability, mood changes, hunger, weakness, or feeling jittery.
Serious allergic reactions. Stop using Foundayo and get medical help right away if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, or very rapid heartbeat.
Changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with Foundayo.
Gallbladder problems. Gallbladder problems have happened in some people who use Foundayo.
