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
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.
Eli Lilly (NYSE:LLY) ha annunciato i risultati del trial di fase 3 ATTAIN-1 di orforglipron, un agonista orale del recettore GLP-1 sperimentale per il trattamento dell'obesità. La pillola assunta una volta al giorno ha mostrato una perdita di peso significativa, con i partecipanti che hanno assunto la dose più alta (36 mg) che hanno ottenuto una riduzione media di 27,3 libbre (12,4%) a 72 settimane.
I principali risultati includono: 59,6% dei partecipanti alla dose più alta hanno perso ≥10% del peso corporeo, 39,6% hanno perso ≥15%, e tra i partecipanti con prediabete, fino a 91% hanno raggiunto livelli di glucosio nel sangue quasi normali rispetto al 42% con placebo. Il farmaco ha mostrato miglioramenti significativi nei fattori di rischio cardiovascolare, riducendo i livelli di hsCRP del 47,7%.
Il profilo di sicurezza è in linea con la classe GLP-1, con eventi avversi principalmente di natura gastrointestinale. Lilly prevede presentazioni regolatorie globali per il trattamento dell'obesità, con un'approvazione potenziale già il prossimo anno, seguita dalla presentazione per il diabete di tipo 2 nel 2026.
Eli Lilly (NYSE:LLY) anunció los resultados de la fase 3 ATTAIN-1 para orforglipron, un agonista oral del receptor GLP-1 en investigación para el tratamiento de la obesidad. La píldora de uso diario demostró una pérdida de peso significativa, con los participantes que tomaron la dosis más alta (36 mg) logrando una reducción promedio de 27,3 lb (12,4%) a las 72 semanas.
Entre los hallazgos clave se destaca: 59,6% de los participantes con la dosis más alta perdieron ≥10% de su peso corporal, 39,6% perdieron ≥15%, y entre los participantes con prediabetes, hasta 91% lograron niveles de glucosa casi normales en comparación con el 42% del placebo. El fármaco mostró mejoras significativas en factores de riesgo cardiovascular, reduciendo los niveles de hsCRP en 47,7%.
El perfil de seguridad se alineó con la clase GLP-1, con eventos adversos principalmente gastrointestinales. Lilly planea presentaciones regulatorias globales para el tratamiento de la obesidad, con una posible aprobación ya el año próximo, seguida de la presentación para la diabetes tipo 2 en 2026.
Eli Lilly (NYSE:LLY)가 체질량지수 조절을 위한 연구용 경구 GLP-1 수용체 작용제인 orforglipron의 3상 ATTAIN-1 시험 결과를 발표했습니다. 하루 한 번 복용하는 알약은 유의미한 체중 감소를 보여주었으며, 가장 높은 용량인 36 mg를 투여한 참가자들은 72주 차에 평균 27,3 lb(12,4%)의 감소를 달성했습니다.
주요 결과로는 가장 높은 용량의 참가자 중 59,6%가 체중의 ≥10%를 잃었고, 39,6%가 ≥15%를 잃었으며, 당뇨전단계(prediabetes) 참가자 중 최대 91%가 포도당 수치를 거의 정상으로 회복했고 위약군은 42%였습니다. 이 약물은 hsCRP 수치를 47,7% 감소시키는 등 심혈관 위험 요인에서도 의미 있는 개선을 보였습니다.
안전성 프로파일은 GLP-1 계열과 일치했고 주로 위장관 관련 부작용이 있었습니다. Lilly는 비만 치료제에 대한 글로벌 규제 제출을 계획하고 있으며 내년 이른 시일에 승인 가능성이 있으며, 이후 2026년에는 제2형 당뇨병 제출이 예정되어 있습니다.
Eli Lilly (NYSE:LLY) a annoncé les résultats de l’étude de phase 3 ATTAIN-1 pour l’orforglipron, un agoniste oral du récepteur GLP-1 expérimental destiné au traitement de l’obésité. Cette pilule à prise quotidienne a montré une perte de poids significative, les participants utilisant la dose la plus élevée (36 mg) obtenant une réduction moyenne de 27,3 lb (12,4%) à 72 semaines.
Parmi les résultats clés: 59,6% des participants à la dose maximale ont perdu ≥10% de leur poids corporel, 39,6% ont perdu ≥15%, et chez les personnes prédiabétiques, jusqu’à 91% ont atteint des niveaux de glucose quasi normaux par rapport à 42% sous placebo. Le médicament a montré des améliorations significatives des facteurs de risque cardiovasculaire, avec une réduction des hsCRP de 47,7%.
Le profil de sécurité était aligné sur la classe GLP-1, avec des effets indésirables principalement gastro-intestinaux. Lilly prévoit des soumissions réglementaires mondiales pour le traitement de l’obésité, avec une éventuelle approbation dès l’année prochaine, suivie d’une soumission pour le diabète de type 2 en 2026.
Eli Lilly (NYSE:LLY) gab Ergebnisse der Phase-3-Studie ATTAIN-1 zu Orforglipron bekannt, einem erforschten oralen GLP-1-Rezeptor-Agonisten zur Behandlung von Fettleibigkeit. Die täglich einzunehmende Tablette zeigte signifikanten Gewichtsverlust, wobei die höchste Dosis (36 mg) eine durchschnittliche Reduktion von 27,3 lb (12,4%) nach 72 Wochen erreichte.
Zu den wichtigsten Befunden gehört: 59,6% der Teilnehmer mit der höchsten Dosierung verloren ≥10% des Körpergewichts, 39,6% verloren ≥15%, und bei Teilnehmern mit Prädiabetes erreichten bis zu 91% nahezu normale Blutzuckerwerte im Vergleich zu 42% mit Placebo. Das Medikament zeigte bedeutende Verbesserungen bei kardiovaskulären Risikofaktoren, mit einer Reduktion des hsCRP-Werts um 47,7%.
Das Sicherheitsprofil entsprach der GLP-1-Klasse, überwiegend gastrointestinale Nebenwirkungen. Lilly plant globale regulatorische Einreichungen für die Behandlung von Fettleibigkeit, mit einer möglichen Zulassung bereits im nächsten Jahr, gefolgt von einer Einreichung für Typ-2-Diabetes im Jahr 2026.
إيلي ليلي (NYSE:LLY) أعلنت عن نتائج تجربة المرحلة الثالثة ATTAIN-1 لعقار أوفورغليبرون، وهو مُحفِّز لمستقبل GLP-1 فموي قيد البحث لعلاج السمنة. حبة يومية تُظهر فقدان وزن كبير، حيث حقق المشاركون الذين تناولوا أعلى جرعة (36 ملغ) انخفاضاً متوسطاً قدره 27.3 رطلاً (12.4%) في 72 أسبوعاً.
تشمل النتائج الرئيسية: 59.6% من المشاركين على أعلى جرعة فقدوا ≥10% من وزنهم، و39.6% فقدوا ≥15%، وبالنسبة للمشاركين المصابين بما قبل السكري، حقق حتى 91% منهم مستويات سكر قريبة من الطبيعي مقارنة بـ 42% في الدواء الوهمي. وأظهر الدواء تحسناً معنوياً في عوامل الخطورة القلبية الوعائية، مع تخفيض مستويات hsCRP بنسبة 47.7%.
الملفّ السلامي آمن ومتوافق مع فئة GLP-1، مع أحداث جانبية تتعلق بالجهاز الهضمي في الأساس. تخطط ليلي لإرسال طلبات تنظيمية عالمية لعلاج السمنة، مع إمكان الحصول على موافقة في العام المقبل، يتبعها تقديم لمرض السكري من النوع 2 في 2026.
Eli Lilly (NYSE:LLY) 宣布了用于减肥的口服 GLP-1 受体激动剂 ORFORGLIPRON 的 III 期 ATTAIN-1 试验结果。每日一次的药片显示出显著的体重减轻，服用最高剂量（36 mg）的参与者在72周时平均减少了 27.3 磅（12.4%）。
关键发现包括：最高剂量组有 59.6% 的参与者减重 ≥10%，39.6% 减重 ≥15%，而糖耐量异常者（糖尿病前期）中高达 91% 达到了接近正常的血糖水平，相比之下安慰剂组为 42%。该药在心血管风险因素方面也显示出显著改善，hsCRP 水平降低了 47.7%。
安全性特征与 GLP-1 类一致，主要为胃肠道相关不良反应。礼来公司计划就肥胖治疗提交全球监管申请，最早可能在明年获得批准，随后在 2026 年提交 2 型糖尿病治疗相关申请。
- 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
- 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%)
Insights
Lilly's oral GLP-1 shows impressive 12.4% weight loss and strong cardiometabolic improvements, positioning it as a potential first-line obesity treatment.
Eli Lilly's Phase 3 ATTAIN-1 trial results for orforglipron present compelling evidence for this investigational once-daily oral GLP-1 receptor agonist. At the highest dose (36mg), patients achieved an average weight loss of 27.3 pounds (12.4%) at 72 weeks using the efficacy estimand. The data shows a clear dose-response relationship across the three tested doses (6mg, 12mg, and 36mg).
Particularly noteworthy is the proportion of patients achieving significant weight thresholds: 59.6% lost ≥10% of body weight and 39.6% lost ≥15% at the highest dose. These results position orforglipron competitively within the GLP-1 class, though slightly below the efficacy seen with injectable semaglutide or tirzepatide.
Beyond weight loss, the cardiometabolic improvements are clinically meaningful. The drug demonstrated significant reductions in non-HDL cholesterol (8.5%), triglycerides (21.6%), and systolic blood pressure (6.7 mmHg) at the highest dose. The 47.7% reduction in hsCRP—a marker of inflammation—is particularly impressive as inflammation is increasingly recognized as a key pathway in obesity-related complications.
Perhaps most striking is that 91% of prediabetic participants returned to normoglycemia compared to 42% on placebo, suggesting potential for diabetes prevention. The safety profile aligns with the GLP-1 class, with primarily gastrointestinal adverse events and no hepatic safety signals—a critical differentiation from earlier oral weight loss medications.
As the first potential oral GLP-1 for obesity, orforglipron could substantially expand the addressable market by offering a more convenient alternative to injections, potentially becoming a first-line option in primary care settings where most obesity is managed.
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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