Lilly's Triple Agonist, Retatrutide, Delivered Powerful Weight Loss in Pivotal Phase 3 Obesity Trial

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INDIANAPOLIS, May 21, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), today announced positive topline results from TRIUMPH-1, a Phase 3 clinical 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 obesity or overweight and at least one weight-related comorbidity and without diabetes. At 80 weeks, all doses of retatrutide (4 mg, 9 mg, and 12 mg) met the primary and key secondary endpoints for obesity, delivering clinically meaningful weight loss.

  • In TRIUMPH-1, participants on 12 mg retatrutide lost an average of 70.3 lbs (28.3%) over 80 weeks with 45.3% of participants achieving ≥30% weight loss, a level long associated with bariatric surgery
  • Individuals with a baseline BMI ≥35 who participated in a study extension continued to lose weight, and achieved up to an average of 85.0 lbs (30.3%) weight loss at 104 weeks
  • At the 4 mg dose, reached with only a single escalation step, participants lost an average of 47.2 lbs (19.0%) at 80 weeks with a lower observed discontinuation rate due to adverse events vs. placebo

    • "Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease," 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. "It was impressive to see that every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants, and people with severe obesity on the highest dose lost on average 30% of their body weight over two years. Importantly, treatment with retatrutide not only resulted in robust weight reduction, but also in clear improvements in assessed cardiometabolic health measures. For patients I see in clinic, retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory."

    For the primary endpoint, participants taking retatrutide 9 mg and 12 mg lost an average of 64.4 lbs (25.9%) and 70.3 lbs (28.3%), respectively. Those taking the 4 mg dose of retatrutide, with just a single dose escalation step, lost an average of 47.2 lbs (19.0%). Notably, 65.3% of participants taking retatrutide 12 mg achieved a BMI <30, falling under the threshold for obesity at 80 weeks, including 37.5% of those who started with class 3 obesity (BMI ≥40).1 In a pre-specified blinded extension for those with a BMI ≥35, participants who continued on retatrutide 12 mg to 104 weeks lost an average of 85.0 lbs (30.3%).2 Additionally, retatrutide showed significant improvements from baseline across certain cardiovascular risk factors, including waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein (hsCRP).

    TRIUMPH-1 Efficacy Estimand Results3

    Primary Endpoint at 80 Weeks

    Retatrutide 4 mg

    Retatrutide 9 mg

    Retatrutide 12 mg

    Placebo

    Percent change in body weight at 80 weeks from avg. baseline of 112.7 kg (248.5 lbs; BMI of 40.0 kg/m2)i

    -19.0%

    (-21.4 kg;

    -47.2 lbs)

    -25.9%

    (-29.2 kg;

    -64.4 lbs)

    -28.3%

    (-31.9 kg;

    -70.3 lbs)

    -2.2%

    (-2.5 kg;

    -5.5 lbs)

    Key Secondary Endpoints at 80 Weeks

    Change in waist circumference from baseline of 118.3 cm (46.6 in)

    -16.3 cm (-6.4 in)

    -21.8 cm (-8.6 in)

    -24.1 cm (-9.5 in)

    -3.6 cm (-1.4 in)

    Percent of participants achieving body weight reduction of ≥25%

    27.8 %

    52.9 %

    62.5 %

    2.2 %

    Percent of participants achieving body weight reduction of ≥30%

    15.3 %

    37.9 %

    45.3 %

    0.5 %

    Percent of participants achieving body weight reduction of ≥35%

    5.9 %

    20.8 %

    27.2 %

    0.3 %

    Pre-specified Extension at 104 Weeksii

    Retatrutide 4 mg to MTDiii

    Retatrutide 9 mg to MTDiii

    Retatrutide 12 mg to MTDiii

    Placebo to Retatrutide MTDiii

    Percent change in body weight at 104 weeks from avg. baseline of 121.7 kg (268.3 lbs; BMI of 42.8 kg/m2)

    -27.9%

    (-33.2 kg;

    -73.3 lbs)

    -29.5%

    (-36.6 kg;

    -80.7 lbs)

    -30.3%

    (-38.5 kg;

    -85.0 lbs)

    -19.2%

    (-22.6 kg;

    -49.9 lbs)

    iPercent body weight reduction with retatrutide 4 mg was a key secondary endpoint.iiThe extension period enrolled 532 participants with BMI ≥35 at baseline who had completed the main 80-week study and tolerated their assigned dose of medication. iiiParticipants in the trial extension received retatrutide at a maximum tolerated dose of 9 mg or 12 mg.

    "TRIUMPH-1 highlights the importance of options and the potential for retatrutide to help people across various stages of their obesity journey," said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. "From the 4 mg dose, reaching nearly 20% weight loss with one escalation step, to the 12 mg dose that delivered a level of weight loss long associated with bariatric surgery, retatrutide offers the potential for a patient-centric approach to obesity.4 Together with Zepbound and Foundayo, retatrutide could build on Lilly's commitment to match treatments to the needs and preferences of patients."

    For the treatment-regimen estimand, each dose level of retatrutide led to improvements across the primary and key secondary endpoints, as well as the pre-specified extension, including:5

  • Percent change in body weight at 80 weeks: -17.6% (-19.8 kg; -43.7 lbs; 4 mg); -23.7% (-26.7 kg; -58.9 lbs; 9 mg); -25.0% (-28.2 kg; -62.1 lbs; 12 mg) and -3.9% (-4.4 kg; -9.7 lbs; placebo)
  • Percent change in body weight at 104 weeks: -25.7% (-30.6 kg; -67.5 lbs; 4 mg to MTD); -28.7% (-35.6 kg; -78.4 lbs; 9 mg to MTD); -29.9% (-38.1 kg; -83.9 lbs; 12 mg to MTD) and -18.9% (-22.3 kg; -49.1 lbs; placebo to MTD)

    • The types of adverse events seen were generally consistent with trials of other incretin-based therapies. The most common adverse events among participants treated with retatrutide (4 mg, 9 mg, 12 mg, vs. placebo, respectively) were nausea (28.6%, 38.4% and 42.4% vs. 14.8%), diarrhea (25.2%, 34.1% and 32.0% vs. 13.5%), constipation (23.8%, 25.9% and 26.1% vs. 10.9%), vomiting (10.6%, 22.8% and 25.3% vs. 4.8%), and upper respiratory tract infection (14.2%, 12.2% and 13.1% vs. 11.6%). Incidences of dysesthesia occurred in 5.1%, 12.3%, and 12.5% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 0.9% with placebo, and incidences of urinary tract infections occurred in 7.5%, 8.8%, and 8.4% of patients treated with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 5.3% with placebo. Events of dysesthesia and urinary tract infections 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%, 11.3%, with retatrutide 4 mg, 9 mg, and 12 mg, respectively, compared with 4.9% with placebo.

    Additional TRIUMPH-1 results will be presented at the 86th annual American Diabetes Association Scientific Sessions, along with other results from Lilly's cardiometabolic pipeline. Additional detailed results will be presented at future medical meetings and published in peer-reviewed journals. More results from the TRIUMPH Phase 3 clinical trial program will be shared later this year, including data from TRIUMPH-2, which is evaluating retatrutide in adults with obesity or overweight and type 2 diabetes, and TRIUMPH-3, which is evaluating retatrutide in adults with obesity or overweight and established cardiovascular disease.

    About retatrutideRetatrutide is an investigational, once-weekly, triple hormone receptor agonist, which 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 OSA, 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 programTRIUMPH‑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). Data described in this press release refer to the master trial and extension period; analyses of the two basket trials for knee osteoarthritis pain and moderate-to-severe obstructive sleep apnea will be released subsequently.

    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.

    Endnotes and References

  • The proportion of participants achieving BMI <30 was a pre-specified analysis not controlled for multiplicity; the same endpoint among participants with a baseline BMI ≥40 was assessed post-hoc.
  • The pre-specified extension enrolled the first 532 participants from participating countries to complete Week 80 on study drug without discontinuation or permanent dose reduction, with BMI ≥35 at baseline and >22 at Week 80. Their follow-up continued for 24 additional weeks targeting the achievement of retatrutide MTD (9 or 12 mg once weekly), for up to 104 weeks total treatment. All original arms are eligible to preserve blinding.
  • 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.
  • Courcoulas AP, Yanovski SZ, Bonds D, et al. Long-term outcomes of bariatric surgery: a National Institutes of Health symposium. JAMA Surg. 2014;149(12):1323-1329.
  • The treatment-regimen estimand represents the average treatment effect regardless of adherence to study intervention or initiation of prohibited weight management treatments.

    • 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 nearly 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.

    Cautionary Statement Regarding Forward-Looking StatementsThis 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 obesity or overweight and at least one weight-related comorbidity, 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 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.

    SOURCE Eli Lilly and Company

    Source: HealthDay

    Retatrutide FDA Approval History

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    Posted : 2026-05-22 09:54

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