In TRIUMPH-2, adults with obesity or overweight and type 2 diabetes, a population with increased difficulties losing weight, lost up to an average of 49.6 lbs (20.8%) at 80 weeks

In TRIUMPH-3, adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes, lost up to an average of 55.8 lbs (22.6%) at 80 weeks

Lilly plans to submit a Biologics License Application (BLA) for retatrutide to FDA in Q1 2027

INDIANAPOLIS, July 23, 2026 /PRNewswire/ — Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), today announced positive topline results from TRIUMPH-2 and TRIUMPH-3, two pivotal Phase 3 trials evaluating retatrutide, an investigational, first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist. In both studies, retatrutide met the primary endpoint, delivering substantial weight loss in adults with obesity and some of its most serious complications: type 2 diabetes and established cardiovascular disease.

“Across five positive Phase 3 studies, retatrutide has shown powerful efficacy, and we believe it could be an important future tool in the management of cardiometabolic health,” said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. “With the positive results from TRIUMPH-2 and TRIUMPH-3, we now have the clinical data package to support global submissions for retatrutide as a potential treatment for obesity, knee osteoarthritis pain, and obstructive sleep apnea. We look forward to working with regulators as they evaluate this first-of-its-kind medicine.”

In TRIUMPH-2, all three studied doses of retatrutide (4 mg, 9 mg, and 12 mg) delivered substantial weight loss and improved glycemic control at 80 weeks in adults with type 2 diabetes and obesity or overweight. 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, alongside A1C reductions of up to an average of 1.6%.

In TRIUMPH-3, both studied doses of retatrutide (9 mg and 12 mg) delivered substantial weight loss in adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes. Participants lost up to an average of 55.8 lbs (22.6%) at 80 weeks.

In the study, major adverse cardiovascular events (MACE) occurred less frequently than anticipated in both retatrutide and placebo arms. In pre-specified analyses for time to first occurrence of MACE, there were 44 MACE-5 (all-cause death, heart attack, stroke, heart failure event, or coronary revascularization) events observed in participants randomized to retatrutide (pooled 9 mg and 12 mg) and 52 events observed in those randomized to placebo, resulting in a hazard ratio of 0.82 (95.0% CI: 0.55 to 1.22). There were 27 MACE-3 (cardiovascular death, heart attack, or stroke) events in participants randomized to retatrutide and 23 in those randomized to placebo, resulting in a hazard ratio of 1.12 (95.0% CI: 0.64 to 1.96).

In TRIUMPH-3, retatrutide meaningfully reduced certain cardiovascular risk factors, with the highest dose delivering average reductions of 37.0% in triglycerides, 16.5% in non-HDL cholesterol, 9.3 mmHg in systolic blood pressure, 7.5 in (19.0 cm) in waist circumference, and 51.2% in high-sensitivity C-reactive protein (hsCRP).

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%). In TRIUMPH-3, the most common adverse events with retatrutide (9 mg, 12 mg vs. placebo, respectively) were diarrhea (30.1%, 24.4% vs. 8.7%), nausea (21.7%, 22.4% vs. 5.8%), constipation (18.0%, 15.7% vs. 7.1%), decreased appetite (13.5%, 14.5% vs. 3.0%), and hyperglycemia (3.9%, 3.1% vs. 13.4%). In TRIUMPH-2, the incidence 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. In TRIUMPH-3, the incidence of dysesthesia and urinary tract infections were 6.4%, 6.4% vs. 1.3% and 6.1%, 7.0% vs. 5.3% with retatrutide 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. Discontinuation rates due to adverse events in TRIUMPH-3 were 9.8% (9 mg) and 13.5% (12 mg) with retatrutide, compared with 4.8% for placebo.

Detailed results from TRIUMPH-2 and TRIUMPH-3 will be presented at future medical meetings and published in peer-reviewed journals. Lilly is completing the comprehensive Chemistry, Manufacturing, and Controls (CMC) data package required for a Biologics License Application (BLA) and plans to subsequently submit retatrutide in Q1 2027 for U.S. approval.

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, TRIUMPH-3, 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. 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 steps at 2 mg and 4 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 four weeks.

TRIUMPH-3 (NCT05882045) is a Phase 3, 80-week, randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of retatrutide once weekly compared with placebo in participants with severe obesity (Class 2 or Class 3), defined as BMI ≥35 kg/m², and established cardiovascular disease. The study randomized 1,949 participants in a 1:1:2 ratio to receive retatrutide 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 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 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 obstructive sleep apnea and obesity, and knee osteoarthritis pain across four global registrational trials. The program, which began in 2023, enrolled more than 5,800 participants.

Endnotes:

1. The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and modifications) without initiating prohibited weight management treatments (and glycemic rescue therapy for glycemic endpoints only).

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. 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

• Tell your healthcare provider about all the medicines you take. Foundayo may affect the way some medicines work, and some medicines may affect the way Foundayo works.
• Pregnancy Exposure Registry: There will be a pregnancy exposure registry for women who have taken Foundayo during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry, or you may contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979).
• If you take birth control pills by mouth, talk to your healthcare provider before you take Foundayo. Birth control pills may not work as well while taking Foundayo. Your healthcare provider may recommend another type of birth control for 30 days after starting Foundayo and for 30 days after each dose increase of Foundayo.
• Talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking medicines to treat diabetes including an insulin or sulfonylurea.

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

• Take Foundayo exactly as your healthcare provider tells you to.
• Use Foundayo with a reduced-calorie diet and increased physical activity.
• Take Foundayo by mouth 1 time each day, with or without food.
• Swallow tablets whole. Do not break, crush, or chew the tablet.
• If you miss a dose, take it as soon as possible. Do not take 2 doses of Foundayo in the same day.
• Do not take more than 1 tablet per day.
• If you miss taking Foundayo for 7 or more days in a row, call your healthcare provider to talk about how to restart your treatment.
• If you take too much Foundayo, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.

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. 

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:

• obesity, or some adults with overweight who also have weight-related medical problems, to lose excess body weight and keep the weight off. 
• moderate-to-severe obstructive sleep apnea (OSA) and obesity to improve their OSA.

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.

• Do not use Zepbound if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).
• Do not use Zepbound if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Do not use Zepbound if you have had a serious allergic reaction to tirzepatide or any of the ingredients in Zepbound.

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

• Your healthcare provider should show you how to use Zepbound before you use it for the first time. 
• Talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking medicines to treat diabetes including an insulin or sulfonylurea.
• If you take birth control pills by mouth, talk to your healthcare provider before you use Zepbound. Birth control pills may not work as well while using Zepbound. Your healthcare provider may recommend another type of birth control for 4 weeks after you start Zepbound and for 4 weeks after each increase in your dose of 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.

• Pregnancy Exposure Registry: There will be a pregnancy exposure registry for women who have taken Zepbound during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry, or you may contact Lilly at 1-800-LillyRx (1-800-545-5979).

How to take

• Read the Instructions for Use that come with Zepbound.
• Use Zepbound exactly as your healthcare provider says.
• Use Zepbound with a reduced-calorie diet and increased physical activity.
• Inject Zepbound under the skin (subcutaneously) of your stomach (abdomen), thigh, or have another person inject in the back of the upper arm. Do not inject ZEPBOUND into a muscle (intramuscularly) or vein (intravenously).
• Use Zepbound 1 time each week, at any time of the day.
• Change (rotate) your injection site with each weekly injection. Do not use the same site for each injection.

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 goto 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
Zepbound®, its delivery device base and KwikPen® are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

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

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. 

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 and obesity or overweight and adults with severe obesity and established cardiovascular disease, 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.

Refer to:  Niki Biro; [email protected] (Media)
                 Michael Czapar; [email protected] (Investors)

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SOURCE Eli Lilly and Company