Lilly's oral GLP-1, orforglipron, demonstrated superior glycemic control in two successful Phase 3 trials, reconfirming its potential as a foundational treatment in type 2 diabetes
Eli Lilly (NYSE: LLY) reported positive topline Phase 3 results for oral GLP-1 orforglipron from ACHIEVE-2 and ACHIEVE-5 on Oct 15, 2025. At week 40, orforglipron doses (3 mg, 12 mg, 36 mg) met primary and all key secondary endpoints for both efficacy and treatment-regimen estimands, delivering meaningful A1C reductions and weight loss versus comparators.
Key numeric results: ACHIEVE-2 A1C change vs dapagliflozin (efficacy estimand) was -1.3%/ -1.7%/ -1.7% (3/12/36 mg) vs -0.8%; ACHIEVE-5 with insulin glargine showed -1.5%/ -2.1%/ -1.9% vs -0.8% for placebo. Safety was consistent with prior studies; common adverse events were GI-related and generally mild-to-moderate.
Lilly expects ACHIEVE-4 readout in Q1 2026 and plans regulatory submissions for type 2 diabetes in 2026; obesity submission remains on track for year-end.
Eli Lilly (NYSE: LLY) ha riportato risultati positivi di topline di fase 3 per l'GLP-1 orale orforglipron provenienti dagli studi ACHIEVE-2 e ACHIEVE-5 il 15 ottobre 2025. Alla settimana 40, le dosi di orforglipron (3 mg, 12 mg, 36 mg) hanno raggiunto l'obiettivo primario e tutti i principali endpoint secondari sia per l'efficacia sia per gli estimatori del regime di trattamento, offrendo significative A1C riduzioni e perdita di peso rispetto ai confronti.
Risultati numerici chiave: la variazione di A1C in ACHIEVE-2 rispetto alla dapagliflozina (estimand efficacia) era -1.3%/ -1.7%/ -1.7% (3/12/36 mg) vs -0.8%; ACHIEVE-5 con insulina glargina ha mostrato -1.5%/ -2.1%/ -1.9% vs -0.8% per placebo. La sicurezza era coerente con gli studi precedenti; gli eventi avversi comuni erano di origine GI e generalmente lievi-moderati.
Lilly prevede la pubblicazione di ACHIEVE-4 nel primo trimestre del 2026 e ha in programma presentazioni regolatorie per il diabete di tipo 2 nel 2026; la presentazione per l'obesità rimane in linea con i tempi previsti per la fine dell'anno.
Eli Lilly (NYSE: LLY) informó resultados positivos de topline de fase 3 para GLP-1 oral orforglipron de ACHIEVE-2 y ACHIEVE-5 el 15 de octubre de 2025. A la semana 40, las dosis de orforglipron (3 mg, 12 mg, 36 mg) cumplieron con el objetivo primario y todos los endpoints secundarios clave tanto para la eficacia como para los estimadores del régimen de tratamiento, logrando reducciones significativas de A1C y pérdida de peso frente a los comparadores.
Resultados numéricos clave: el cambio de A1C en ACHIEVE-2 respecto a dapagliflozina (estimador de eficacia) fue -1.3%/ -1.7%/ -1.7% (3/12/36 mg) vs -0.8%; ACHIEVE-5 con insulina glargina mostró -1.5%/ -2.1%/ -1.9% vs -0.8% para placebo. La seguridad fue consistente con los estudios anteriores; los eventos adversos comunes fueron de origen GI y generalmente leves a moderados.
Lilly espera la lectura de ACHIEVE-4 en el primer trimestre de 2026 y planea presentaciones regulatorias para diabetes tipo 2 en 2026; la presentación para obesidad continúa en camino para fin de año.
Eli Lilly (NYSE: LLY)는 ACHIEVE-2 및 ACHIEVE-5의 경구용 GLP-1 orforglipron에 대한 긍정적 상반기 3상 topline 결과를 2025년 10월 15일 발표했습니다. 40주 차에서 orforglipron 용량(3 mg, 12 mg, 36 mg)은 효능 추정치와 치료-요법 추정치 모두에서 1차 및 모든 주요 2차 항목을 충족했으며, 비교군에 비해 의미 있는 A1C 감소와 체중 감소를 달성했습니다.
주요 수치 결과: ACHIEVE-2의 dapagliflozin 대비 A1C 변화(효능 추정치)는 -1.3%/ -1.7%/ -1.7% (3/12/36 mg)로, -0.8%과 비교됩니다; ACHIEVE-5에서 인슐린 글라진과 함께는 -1.5%/ -2.1%/ -1.9%를 보였고 위약은 -0.8%이었습니다. 안전성은 이전 연구와 일치했으며 일반적으로 경증-중등도인 GI 관련 일반적 이상반응이 있었습니다.
릴리는 ACHIEVE-4의 2026년 1분기 발표를 예상하고 2026년 당뇨병 2형에 대한 규제 제출을 계획하고 있습니다; 비만 관련 제출은 연말 목표를 유지하고 있습니다.
Eli Lilly (NYSE: LLY) a partagé des résultats positifs de topline de phase 3 pour le GLP-1 oral orforglipron issus des essais ACHIEVE-2 et ACHIEVE-5 le 15 octobre 2025. À la semaine 40, les doses d'orforglipron (3 mg, 12 mg, 36 mg) ont atteint l'objectif primaire et tous les principaux endpoints secondaires pour l'efficacité et les estimations du régime de traitement, générant des réductions significatives de A1C et une perte de poids par rapport aux comparateurs.
Principaux résultats numériques : la variation d'A1C dans ACHIEVE-2 par rapport à la dapagliflozine (estimand efficacité) était de -1.3%/ -1.7%/ -1.7% (3/12/36 mg) contre -0.8%; ACHIEVE-5 avec de l'insuline glargine a montré -1.5%/ -2.1%/ -1.9% contre -0.8% pour le placebo. La sécurité était conforme aux études précédentes ; les événements indésirables courants étaient d'origine GI et généralement légers à modérés.
Lilly prévoit la présentation d'ACHIEVE-4 au T1 2026 et prévoit des soumissions réglementaires pour le diabète de type 2 en 2026 ; la soumission pour l'obésité reste sur la bonne voie pour la fin de l'année.
Eli Lilly (NYSE: LLY) meldete positive Topline-Ergebnisse der Phase-3-Studien für das orale GLP-1 orforglipron aus ACHIEVE-2 und ACHIEVE-5 am 15. Oktober 2025. In Woche 40 erfüllten die orforglipron-Dosen (3 mg, 12 mg, 36 mg) sowohl primäre als auch alle wichtigen sekundären Endpunkte für Wirksamkeit und Behandlungsregime-Estimanden und führten zu deutlichen A1C-Verkürzungen und Gewichtsverlust gegenüber den Vergleichspräparaten.
Wichtige numerische Ergebnisse: ACHIEVE-2 A1C-Veränderung gegenüber Dapagliflozin (Wirksamkeit estimand) betrug -1.3%/ -1.7%/ -1.7% (3/12/36 mg) vs -0.8%; ACHIEVE-5 mit Insulin Glargin zeigte -1.5%/ -2.1%/ -1.9% vs -0.8% für Placebo. Die Sicherheit war konsistent mit früheren Studien; häufige unerwünschte Ereignisse waren GI-bedingt und im Allgemeinen mild bis moderat.
Die Lilly erwartet die ACHIEVE-4-Daten im Q1 2026 und plant Zulassungsanträge für Typ-2-Diabetes im Jahr 2026; der Antrag für Adipositas bleibt auf dem Zeitplan für das Jahresende.
إيليليلي (NYSE: LLY) أعلنت عن نتائج إيجابية من خط الأساس في المرحلة 3 لـ GLP-1 الشفوي orforglipron من دراستي ACHIEVE-2 و ACHIEVE-5 في 15 أكتوبر 2025. في الأسبوع 40، حقنت جرعات orforglipron (3 mg، 12 mg، 36 mg) الهدف الأول وجميع النقاط الثانوية الرئيسية لكلا مقاييس الفعالية ونمط العلاج، محققة انخفاضات معنوية في A1C وفقدان وزن مقارنةً بالمقارنة.
النتائج الرقمية الأساسية: التغيير في A1C في ACHIEVE-2 مقارنةً بـ dapagliflozin (المقدر الفعّال) كان -1.3%/ -1.7%/ -1.7% (3/12/36 mg) مقابل -0.8%; ACHIEVE-5 مع جلاتر-إين كان -1.5%/ -2.1%/ -1.9% مقابل -0.8%Placebo. السلامة كانت متوافقة مع الدراسات السابقة؛ الأحداث السلبية الشائعة كانت GI-متعلقة وبشكل عام خفيفة إلى متوسطة.
تتوقع ليللي إصدار ACHIEVE-4 في الربع الأول من 2026 وتخطّط لتقديمات تنظيمية لمرض السكري من النوع 2 في 2026؛ أما تقديم السمنة فلا يزال على المسار حتى نهاية العام.
Eli Lilly (NYSE: LLY) 于 2025 年 10 月 15 日公布了口服 GLP-1 orforglipron 在 ACHIEVE-2 与 ACHIEVE-5 的 IIIb 期初步结果。第 40 周，orforglipron 的剂量（3 mg、12 mg、36 mg）在疗效与治疗方案估算中均达到了一级及所有关键次级终点，与对照组相比实现了有意义的 A1C 降幅和体重下降。
关键数值结果：ACHIEVE-2 相对于达格列净的 A1C 变化（疗效估算）为 -1.3%/ -1.7%/ -1.7%（3/12/36 mg），相比 -0.8%；ACHIEVE-5 与注射用胰岛素赖汗（insulin glargine）联合显示为 -1.5%/ -2.1%/ -1.9%，对照组为 -0.8%。安全性与先前研究一致；常见不良事件为胃肠道相关，通常轻度至中度。
对于 ACHIEVE-4 的结果预计于 2026 年第一季度公布，计划在 2026 年提交糖尿病 2 型的监管申请；肥胖治疗的提交仍按年度计划推进。
- A1C reduction up to -1.7% vs dapagliflozin -0.8% (ACHIEVE-2)
- A1C reduction up to -2.1% with insulin glargine vs placebo -0.8% (ACHIEVE-5)
- All doses met primary and key secondary endpoints at 40 weeks
- Most common adverse events were gastrointestinal-related (mild-to-moderate)
- Regulatory approval depends on final ACHIEVE-4 readout expected in Q1 2026
Insights
Phase 3 ACHIEVE-2 and ACHIEVE-5 met primary and key secondary endpoints at week 40, showing superior A1C and weight reductions versus active and placebo comparators.
Orforglipron demonstrated A1C reductions up to
These facts imply a clear regulatory data package milestone: topline success across head-to-head and insulin-combination settings supports a 2026 global submission plan stated by the company. Key near-term regulatory dependencies include the planned presentation/publication of full data and results from the final global registration trial, ACHIEVE-4, expected in
Positive commercial positioning: oral GLP-1 shows superiority versus an SGLT-2 and additive benefit with basal insulin, strengthening its market case.
Eli Lilly now positions an oral GLP-1 in direct comparison to a common SGLT-2, reporting greater A1C reductions and weight loss at week
From a commercial lens, the concrete items to monitor are the complete efficacy and tolerability tables in the peer-reviewed publication and the ACHIEVE-4 readout in
In ACHIEVE-2, orforglipron lowered A1C by up to
In ACHIEVE-5, orforglipron lowered A1C by an additional
"Orforglipron has now demonstrated superiority over two active comparators in clinical trials for type 2 diabetes," said Jeff Emmick, M.D., Ph.D., senior vice president of product development, Lilly Cardiometabolic Health. "In ACHIEVE-2, orforglipron outperformed dapagliflozin, a commonly used SGLT-2 therapy, and in ACHIEVE-3, showed greater efficacy than oral semaglutide. The findings from ACHIEVE-5 add to this momentum, showing significant A1C reduction and weight loss when used in combination with titrated basal insulin. Together, these results reinforce orforglipron's potential to become a new standard of care for people living with type 2 diabetes."
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ACHIEVE-2 and ACHIEVE-5 Results |
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ACHIEVE-2 Primary Endpoint |
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Orforglipron |
Orforglipron |
Orforglipron |
Dapagliflozin |
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Change in |
Efficacy |
-1.3 % |
-1.7 % |
-1.7 % |
-0.8 % |
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Treatment- |
-1.2 % |
-1.5 % |
-1.6 % |
-0.8 % |
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ACHIEVE-5 Primary Endpoint |
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Orforglipron |
Orforglipron |
Orforglipron |
Placebo |
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Change in |
Efficacy |
-1.5 % |
-2.1 % |
-1.9 % |
-0.8 % |
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Treatment- |
-1.6 % |
-1.9 % |
-1.8 % |
-0.8 % |
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i All doses of orforglipron achieved statistical significance vs. the comparator, with p<0.001 under both the efficacy and treatment-regimen estimands. |
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ii Insulin glargine doses were adjusted per a treat-to-target algorithm with no restriction from week four to week 40. |
In both trials, the overall safety and tolerability profile of orforglipron, as well as treatment discontinuation rates, were consistent with previous studies. The most common adverse events were gastrointestinal-related and generally mild-to-moderate in severity. No hepatic safety signal was observed.
The detailed results of these trials will be presented at a future medical meeting and published in a peer-reviewed journal. Results are expected in the first quarter of 2026 for ACHIEVE-4, the final global registration trial in the ACHIEVE program. Lilly plans to submit orforglipron for the treatment of type 2 diabetes to global regulatory agencies in 2026, while submission for the treatment of obesity is on track to occur by the end of this year.
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.4 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.5 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, hypertension and osteoarthritis pain in adults with obesity.
About ACHIEVE-2, ACHIEVE-5 and the ACHIEVE clinical trial program
ACHIEVE-2 (NCT06192108) is a Phase 3, 40-week, randomized, active-controlled, open-label study comparing the efficacy and safety of orforglipron 3 mg, 12 mg and 36 mg to dapagliflozin 10 mg in participants with type 2 diabetes and inadequate glycemic control with metformin. The study randomized 962 participants in a 1:1:1:1 ratio to receive either orforglipron 3 mg, 12 mg or 36 mg, or dapagliflozin 10 mg once daily, in addition to background metformin therapy. The objective of the study was to demonstrate that orforglipron is non-inferior in A1C reduction from baseline after 40 weeks, compared to dapagliflozin. Study participants had an A1C between ≥
ACHIEVE-5 (NCT06109311) is a Phase 3, 40-week, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of orforglipron 3 mg, 12 mg and 36 mg in participants with type 2 diabetes and inadequate glycemic control with insulin glargine, with or without metformin and/or SGLT-2 inhibitors. The study randomized 546 participants in a 1:1:1:1 ratio to receive either orforglipron 3 mg, 12 mg or 36 mg, or placebo with background therapy of titrated insulin glargine alone or in combination with metformin and/or SGLT-2 inhibitors. The objective of the study was to demonstrate that orforglipron is superior in A1C reduction from baseline after 40 weeks, compared to placebo. Study participants had an A1C between ≥
The ACHIEVE Phase 3 global clinical development program for orforglipron has enrolled more than 6,000 people with type 2 diabetes across five global registration trials. The program began in 2023, and additional results are anticipated in early 2026.
Endnotes and References
- The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions) without initiating additional antihyperglycemic medications (>14 days of use).
- The treatment-regimen estimand represents the estimated average treatment effect regardless of adherence to study intervention or initiation of additional antihyperglycemic medications.
- Body weight for orforglipron 3 mg vs. dapagliflozin 10 mg was not a primary or key secondary endpoint in ACHIEVE-2.
- 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.
- T. Kawai, B. Sun, H. Yoshino, D. Feng, Y. Suzuki, M. Fukazawa, S. Nagao, D.B. Wainscott, A.D. Showalter, B.A. Droz, T.S. Kobilka, M.P. Coghlan, F.S. Willard, Y. Kawabe, B.K. Kobilka, & K.W. Sloop, 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 type 2 diabetes, Lilly's ability to supply orforglipron, if approved, and the timeline for future 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 type 2 diabetes, 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.
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 references 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.
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Refer to: |
Brooke Frost; brooke.frost@lilly.com; 317-432-9145 (Media) |
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Michael Czapar; czapar_michael_c@lilly.com; 317-617-0983 (Investors) |
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FAQ
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