Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea, demonstrating its remarkable potential to treat obesity and its complications
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
INDIANAPOLIS, June 6, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), today 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.
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 is legally available only to participants in Lilly's clinical trials.
About TRIUMPH-1 and the TRIUMPH clinical trial program
TRIUMPH-1 (NCT05929066) is a Phase 3, 80-week, randomized, double-blind, placebo-controlled master trial comparing the efficacy and safety of retatrutide with placebo in adults with obesity or overweight. TRIUMPH-1 included a master trial for obesity and two basket trials for knee osteoarthritis pain or moderate-to-severe obstructive sleep apnea. The study randomized 2,339 participants in a 1:1:1:1 ratio to receive either 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 step-wise approach every four weeks until reaching the target dose of 4 mg (via one 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-1 included a pre-specified extension period of 104 weeks. The extension period enrolled 532 participants with BMI ≥35 at week 0 who completed the main 80-week study and tolerated their assigned dose of medication. Participants received retatrutide once weekly for an additional 24 weeks, including a blinded escalation to maximum tolerated dose (9 mg or 12 mg).
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, moderate-to-severe 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.
About TRANSCEND-T2D-1 and the TRANSCEND-T2D clinical trial program
TRANSCEND-T2D-1 (NCT06354660) is a Phase 3, 40-week, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of retatrutide with placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study randomized 537 participants in a 1:1:1:1 ratio to receive either retatrutide 4 mg, 9 mg or 12 mg, or placebo. The objective of the study was to demonstrate that retatrutide (4 mg, 9 mg or 12 mg) is superior to placebo in A1C reduction from baseline after 40 weeks, in adults with type 2 diabetes who have not taken any anti-diabetes medications for at least 90 days prior to visit one, and are naïve to insulin therapy except for gestational diabetes. Study participants had A1C between ≥7.0% and ≤9.5% and a BMI of ≥23 kg/m 2 at visit one. Participants randomized to retatrutide initiated treatment with 2 mg once-weekly and increased the dose in a step-wise approach every four weeks until reaching the target dose of 4 mg (via one 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).
The TRANSCEND-T2D Phase 3 clinical trial program is evaluating the safety and efficacy of retatrutide for the treatment of adults with type 2 diabetes across three global registrational trials. The program, which began in 2024, has enrolled more than 2,050 participants and additional results are anticipated over the next year.
Endnotes and References
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.
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.
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. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools.
Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Foundayo may increase the chance of food getting into your lungs during surgery or other procedures. Tell your healthcare providers that you are taking Foundayo before you are scheduled to have surgery or other procedures.
Common side effects
The most common side effects of Foundayo include nausea, constipation, diarrhea, vomiting, indigestion, stomach (abdominal) pain, headache, swollen belly, feeling tired, belching, heartburn, gas, and hair loss. These are not all the possible side effects of Foundayo. Talk to your healthcare provider about any side effect that bothers you or doesn't go away.
Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.
Before taking Foundayo
Review these questions with your healthcare provider:
❑ Do you have other medical conditions, including problems with your pancreas or kidneys, or severe problems with your liver, severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems digesting food?
❑ Do you have a history of diabetic retinopathy?
❑ Are you scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation)?
❑ Are you pregnant or plan to become pregnant? Foundayo may harm your unborn baby.
❑ Are you breastfeeding or plan to breastfeed? Breastfeeding is not recommended during treatment with Foundayo.
❑ Do you take any other prescriptions or over-the-counter medicines, vitamins, or herbal supplements?
How to take
Learn more
Foundayo is a prescription medicine available in 0.8 mg, 2.5 mg, 5.5 mg, 9 mg, 14.5 mg, or 17.2 mg oral tablets. For more information, call 1-800-545-5979 or go to foundayo.lilly.com.
This summary provides basic information about Foundayo but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other healthcare provider about Foundayo and how to take it. Your doctor is the best person to help you decide if Foundayo is right for you.
OG CON BS APR2026
ZEPBOUND INDICATIONS AND SAFETY SUMMARY WITH WARNINGS
Zepbound® (ZEHP-bownd) is an injectable prescription medicine used with a reduced-calorie diet and increased physical activity to help adults with:
Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective for use in children.
Warnings - Zepbound 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.
KwikPen®: Do not share your KwikPen with other people, even if the pen needle has been changed. You may give other people a serious infection or get a serious infection from them.
Zepbound may cause serious side effects, including:
Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Zepbound. 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.
Gallbladder problems. Gallbladder problems have happened in some people who use Zepbound. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), or clay-colored stools.
Inflammation of the pancreas (pancreatitis). Stop using Zepbound 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. You may feel the pain from your abdomen to your back.
Serious allergic reactions. Stop using Zepbound 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.
Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use Zepbound with medicines that can cause low blood sugar, such as a sulfonylurea or insulin. 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.
Changes in vision in patients with type 2 diabetes. Tell your healthcare provider if you have changes in vision during treatment with Zepbound.
Food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). Zepbound may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking Zepbound before you are scheduled to have surgery or other procedures.
Common side effects
The most common side effects of Zepbound include nausea, diarrhea, vomiting, constipation, stomach (abdominal) pain, indigestion, injection site reactions, feeling tired, allergic reactions, belching, hair loss, and heartburn. These are not all the possible side effects of Zepbound. Talk to your healthcare provider about any side effect that bothers you or doesn't go away.
Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.
Before using Zepbound
Review these questions with your healthcare provider:
❑ Do you have other medical conditions, including problems with your pancreas, or severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems digesting food?
❑ Do you take diabetes medicines, such as insulin or sulfonylureas?
❑ Do you have a history of diabetic retinopathy?
❑ Are you scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation)?
❑ Do you take any other prescription medicines or over-the-counter drugs, vitamins, or herbal supplements?
❑ Are you pregnant, plan to become pregnant, breastfeeding, or plan to breastfeed? Zepbound may harm your unborn baby. Tell your healthcare provider if you become pregnant while using Zepbound. Zepbound may pass into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using Zepbound.
How to take
If you take too much Zepbound, call your healthcare provider, call the Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.
Zepbound is approved as a 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg injection.
Learn more
Zepbound is a prescription medicine. For more information, call 1-800-LillyRx (1-800-545-5979) or go to www.zepbound.lilly.com.
This summary provides basic information about Zepbound but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Zepbound and how to take it. Your healthcare provider is the best person to help you decide if Zepbound is right for you.
ZP CON BS 25FEB2026
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about retatrutide as a potential treatment for adults with type 2 diabetes, obesity, and other indications, potential efficacy and tolerability of retatrutide, and the timeline for future readouts, presentations, and other milestones relating to retatrutide and its clinical trials and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with expectations or study results to date, that retatrutide will prove to be a safe and effective treatment for type 2 diabetes, obesity or other potential indications, that retatrutide will receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
Trademarks and Trade Names
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are referenced in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.
Refer to:
Niki Biro; [email protected] (Media)
Michael Czapar; [email protected] (Investors)
SOURCE Eli Lilly and Company