Lilly's oral GLP-1, orforglipron, demonstrated meaningful weight loss and cardiometabolic improvements in complete ATTAIN-1 results published in The New England Journal of Medicine
Rhea-AI Summary
Eli Lilly (NYSE:LLY) announced Phase 3 ATTAIN-1 trial results for orforglipron, an investigational oral GLP-1 receptor agonist for obesity treatment. The once-daily pill demonstrated significant weight loss, with participants taking the highest dose (36mg) achieving an average reduction of 27.3 lbs (12.4%) at 72 weeks.
Key findings include: 59.6% of participants on the highest dose lost ≥10% body weight, 39.6% lost ≥15%, and among participants with prediabetes, up to 91% achieved near-normal blood sugar levels compared to 42% on placebo. The drug showed meaningful improvements in cardiovascular risk factors, reducing hsCRP levels by 47.7%.
Safety profile aligned with the GLP-1 class, with primarily gastrointestinal-related adverse events. Lilly plans global regulatory submissions for obesity treatment, with potential approval as early as next year, followed by type 2 diabetes submission in 2026.
Positive
- Significant weight loss of 27.3 lbs (12.4%) achieved at highest dose
- 91% of prediabetic participants reached near-normal blood sugar levels
- Strong improvements in cardiovascular risk factors including 47.7% reduction in inflammation marker hsCRP
- Convenient once-daily oral administration format
- Safety profile consistent with established GLP-1 class
- Regulatory submission timeline accelerated with potential approval next year
Negative
- Treatment discontinuation rates up to 10.3% due to adverse events at highest dose
- High incidence of gastrointestinal side effects (nausea up to 35.9%, vomiting up to 24%)
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The investigational once-daily oral pill led to an average weight loss of 27.3 lbs (
Orforglipron demonstrated significant improvements across key cardiometabolic risk factors, supporting its potential as a treatment option for millions living with obesity
"Obesity is a complex, global health challenge — and patients need treatment options that are both effective and easy to integrate into everyday life," said Sean Wharton, M.D., director at Wharton Medical Clinic and lead investigator. "In this Phase 3 study, orforglipron demonstrated strong efficacy results and safety consistent with the GLP-1 class, reinforcing its potential as a first-line treatment in primary care. Additionally, orforglipron could help reduce known markers of cardiovascular risk associated with obesity and support meaningful improvements in public health."
In the ATTAIN-1 trial, orforglipron met the primary endpoint of superior body weight reduction compared to placebo, with participants taking the highest dose losing an average of 27.3 lbs (
Full Results | |||||
Orforglipron 6 mg | Orforglipron 12 mg | Orforglipron 36 mg | Placebo
| ||
Primary Endpoint | |||||
Mean percent change in | Efficacy estimand | -
(-8.0 kg; -17.6 lbs) | -
(-9.4 kg; -20.7 lbs) | -
(-12.4 kg; -27.3 lbs) | -
(-1.0 kg; -2.2 lbs) |
Treatment-regimen estimand5 | -
(-7.8 kg; -17.2 lbs) | -
(-8.6 kg; -19.0 lbs) | -
(-11.3 kg; -25.0 lbs) | -
(-2.4 kg; -5.3 lbs) | |
Key Secondary Endpoints | |||||
Percentage of | Efficacy estimand | 63.8 % | 69.3 % | 77.1 % | 22.1 % |
Treatment-regimen estimand | 60.6 % | 63.5 % | 71.8 % | 26.8 % | |
Percentage of | Efficacy estimand | 35.9 % | 45.1 % | 59.6 % | 8.6 % |
Treatment-regimen estimand | 33.3 % | 40.0 % | 54.6 % | 12.9 % | |
Percentage of | Efficacy estimand | 16.5 % | 24.0 % | 39.6 % | 3.6 % |
Treatment-regimen estimand | 15.1 % | 20.3 % | 36.0 % | 5.9 % | |
Percentage of | Efficacy estimand | 7.2 % | 11.4 % | 20.1 % | 1.6 % |
Treatment-regimen estimand | 6.4 % | 9.0 % | 18.4 % | 2.8 % | |
Change in waist circumference from average baseline of 112.4 cm (44.25 in)i | Efficacy estimand | -7.5 cm (-3.0 in) | -9.0 cm (-3.5 in) | -11.1 cm (-4.4 in) | -2.1 cm (-0.8 in) |
Treatment-regimen estimand | -7.1 cm (-2.8 in) | -8.2 cm (-3.2 in) | -10.1 cm (-4.0 in) | -3.1 cm (-1.2 in) | |
Mean percent change in non-HDL cholesterol from baseline of 146.4 mg/dLiii | Efficacy estimand | -5.9 % | -8.3 % | -8.5 % | -1.4 % |
Treatment-regimen estimand | -5.4 % | -7.0 % | -7.7 % | -1.9 % | |
Mean percent change in triglycerides from baseline of 138.8 mg/dLiii | Efficacy estimand | -12.1 % | -15.2 % | -21.6 % | -4.8 % |
Treatment-regimen estimand | -10.4 % | -13.5 % | -20.2 % | -3.8 % | |
Mean change in systolic blood pressure from baseline of 125.5 mm Hgiii | Efficacy estimand | -5.8 mm Hg | -5.9 mm Hg | -6.7 mm Hg | -0.8 mm Hg |
Treatment-regimen estimand | -5.7 mm Hg | -5.1 mm Hg | -6.3 mm Hg | -1.4 mm Hg | |
iControlled for family-wise type 1 error rate.
iiPercentage of participants achieving body weight reductions of ≥
iiiFamily-wise type 1 error rate was controlled for the pooled orforglipron doses compared to the placebo.
"People living with obesity have broad and varied needs — whether it's improving weight, A1C, lipids, blood pressure, or other health markers that primary care physicians routinely address with their patients," said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health. "We're encouraged to see orforglipron improve many of these areas in ATTAIN-1. As a convenient, once-daily pill that can be scaled globally, orforglipron could be ideally suited for early adoption in primary care — where proactive intervention has the potential to lead to meaningful, long-term health improvements."
The safety profile of orforglipron in ATTAIN-1 was consistent with the established GLP-1 receptor agonist class. The most commonly reported adverse events were gastrointestinal-related and generally mild-to-moderate in severity. The most common adverse events for participants treated with orforglipron (6 mg, 12 mg and 36 mg, respectively) were nausea (
Lilly is advancing orforglipron toward global regulatory submissions for the treatment of obesity, with regulatory action expected to occur as early as next year. Submission for the treatment of type 2 diabetes is anticipated in 2026.
About orforglipron
Orforglipron (or-for-GLIP-ron) is an investigational, once-daily small molecule (non-peptide) oral glucagon-like peptide-1 receptor agonist that can be taken any time of the day without restrictions on food and water intake.6 Orforglipron was discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018. Chugai and Lilly published the preclinical pharmacology data of this molecule together.7 Lilly is running Phase 3 studies on orforglipron for the treatment of type 2 diabetes and for weight management in adults with obesity or overweight with at least one weight-related medical problem. It is also being studied as a potential treatment for obstructive sleep apnea and hypertension in adults with obesity.
About ATTAIN-1 and ATTAIN clinical trial program
ATTAIN-1 (NCT05869903) is a Phase 3, 72-week, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of orforglipron 6 mg, 12 mg and 36 mg as a monotherapy to placebo in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease, who did not have diabetes. The trial is the first Phase 3 study of this patient population in which treatment was evaluated as an adjunct to exercise and a balanced, healthy diet rather than a reduced-calorie diet. The trial randomized 3,127 participants across the
The ATTAIN Phase 3 global clinical development program for orforglipron has enrolled more than 4,500 people with obesity or overweight across two global registration trials. The program began in 2023 with additional results anticipated this year.
Endnotes and References
- Percentage of participants achieving body weight reductions of ≥
20% with orforglipron 6 mg was not controlled for family-wise type 1 error rate. - The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and modifications) for 72 weeks without initiating prohibited weight management treatments.
- American Diabetes Association. Standards of Care in Diabetes—2020 Abridged for Primary Care Providers. Clinical Diabetes 2020; 38(1):10–38. https://doi.org/10.2337/cd20-as01
- Not controlled for family-wise type 1 error rate.
- The treatment-regimen estimand represents the estimated average treatment effect regardless of adherence to study intervention or initiation of prohibited weight management treatments.
- Ma X, Liu R, Pratt EJ, Benson CT, Bhattachar SN, Sloop KW. Effect of Food Consumption on the Pharmacokinetics, Safety, and Tolerability of Once-Daily Orally Administered Orforglipron (LY3502970), a Non-peptide GLP-1 Receptor Agonist. Diabetes Ther. 2024 Apr;15(4):819-832. https://doi.org/10.1007/s13300-024-01554-1. Epub 2024 Feb 24. PMID: 38402332; PMCID: PMC10951152.
- Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, Sloop KW. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist, Proc. Natl. Acad. Sci.
U.S.A. 117 (47) 29959-29967, https://doi.org/10.1073/pnas.2014879117 (2020).
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. 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 orforglipron as a potential treatment for adults with obesity or overweight, Lilly's ability to supply orforglipron, if approved, and the timeline for future regulatory submissions, readouts, presentations, and other milestones relating to orforglipron 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 study results to date, that orforglipron will prove to be a safe and effective treatment for obesity or overweight, that orforglipron 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.
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Refer to: | Brooke Frost; brooke.frost@lilly.com; 317-432-9145 (Media) |
Michael Czapar; czapar_michael_c@lilly.com; 317-617-0983 (Investors) |
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