Lilly's oral GLP-1, orforglipron, is successful in third Phase 3 trial, triggering global regulatory submissions this year for the treatment of obesity
Eli Lilly (NYSE:LLY) announced positive Phase 3 ATTAIN-2 trial results for orforglipron, its investigational oral GLP-1 receptor agonist for obesity and type 2 diabetes treatment. The highest dose (36mg) achieved significant weight loss of 22.9 lbs (10.5%) compared to placebo's 5.1 lbs (2.2%) at 72 weeks.
Key achievements include A1C reductions of 1.3% to 1.8% from a baseline of 8.1%, with 75% of participants reaching A1C ≤6.5%. The drug demonstrated improvements in cardiovascular risk factors and reduced inflammation markers by 50.6%. The safety profile aligned with injectable GLP-1 medicines, with primarily mild-to-moderate gastrointestinal side effects.
Following these successful results, Lilly plans to initiate global regulatory submissions for orforglipron's approval as a once-daily oral treatment.
Eli Lilly (NYSE:LLY) ha annunciato risultati positivi di fase 3 dallo studio ATTAIN-2 per orforglipron, il suo candidato orale agonista del recettore GLP-1 per il trattamento dell'obesità e del diabete di tipo 2. La dose più alta (36 mg) ha ottenuto una perdita di peso significativa di 22,9 libbre (10,5%) rispetto a 5,1 libbre (2,2%) del placebo a 72 settimane.
Tra i risultati principali si segnalano riduzioni dell'A1C tra 1,3% e 1,8% partendo da un valore medio baseline di 8,1%, con il 75% dei partecipanti che ha raggiunto A1C ≤6,5%. Il farmaco ha mostrato miglioramenti nei fattori di rischio cardiovascolare e una riduzione dei marker infiammatori del 50,6%. Il profilo di sicurezza è risultato confrontabile a quello dei GLP-1 iniettabili, con effetti collaterali gastrointestinali prevalentemente lievi-moderati.
Alla luce di questi esiti positivi, Lilly intende avviare le domande regolatorie a livello globale per l'approvazione di orforglipron come trattamento orale da assumere una volta al giorno.
Eli Lilly (NYSE:LLY) anunció resultados positivos del ensayo pivotal de fase 3 ATTAIN-2 para orforglipron, su agonista oral del receptor GLP-1 en investigación para la obesidad y la diabetes tipo 2. La dosis más alta (36 mg) logró una pérdida de peso significativa de 22,9 libras (10,5%) frente a 5,1 libras (2,2%) con placebo a las 72 semanas.
Logros clave incluyen reducciones de A1C entre 1,3% y 1,8% desde una línea basal de 8,1%, con el 75% de los participantes alcanzando A1C ≤6,5%. El medicamento mostró mejoras en factores de riesgo cardiovascular y una reducción de marcadores de inflamación del 50,6%. El perfil de seguridad fue comparable al de los GLP-1 inyectables, con efectos gastrointestinales principalmente leves a moderados.
Tras estos resultados favorables, Lilly planea iniciar las presentaciones regulatorias globales para la aprobación de orforglipron como tratamiento oral de administración diaria.
Eli Lilly (NYSE:LLY)는 비만 및 제2형 당뇨병 치료를 위한 경구용 GLP-1 수용체 작용제 후보물질 오르포글립론(orforglipron)의 3상 ATTAIN-2 시험에서 긍정적 결과를 발표했습니다. 가장 높은 용량(36mg)은 72주 시점에서 위약의 5.1파운드(2.2%)에 비해 22.9파운드(10.5%)의 유의한 체중 감소를 달성했습니다.
주요 성과로는 기준치 8.1%에서 출발해 A1C 1.3%~1.8% 감소를 보였고, 참가자의 75%가 A1C ≤6.5%에 도달했습니다. 심혈관 위험 인자 개선과 염증 지표 50.6% 감소도 관찰되었습니다. 안전성 프로파일은 주사형 GLP-1 약물과 유사했으며, 주로 경증~중등도의 위장관계 부작용이 보고되었습니다.
이러한 성공적인 결과를 바탕으로 릴리는 오르포글립론을 하루 1회 복용하는 경구 치료제로 승인받기 위해 글로벌 규제 제출을 시작할 계획입니다.
Eli Lilly (NYSE:LLY) a annoncé des résultats positifs de l'essai de phase 3 ATTAIN-2 pour orforglipron, son agoniste oral du récepteur GLP-1 en développement pour l'obésité et le diabète de type 2. La dose la plus élevée (36 mg) a obtenu une perte de poids significative de 22,9 lb (10,5%) contre 5,1 lb (2,2%) pour le placebo à 72 semaines.
Parmi les points clés figurent des réductions de l'HbA1c de 1,3% à 1,8% depuis une valeur basale de 8,1%, 75% des participants atteignant une HbA1c ≤6,5%. Le médicament a montré des améliorations des facteurs de risque cardiovasculaire et une diminution des marqueurs inflammatoires de 50,6%. Le profil d'innocuité était comparable à celui des GLP-1 injectables, avec des effets gastro-intestinaux principalement légers à modérés.
Suite à ces résultats favorables, Lilly prévoit d'engager des dossiers réglementaires mondiaux pour l'approbation d'orforglipron comme traitement oral une fois par jour.
Eli Lilly (NYSE:LLY) gab positive Ergebnisse der Phase-3-Studie ATTAIN-2 für orforglipron bekannt, seinen oralen GLP-1-Rezeptoragonisten zur Behandlung von Adipositas und Typ-2-Diabetes. Die höchste Dosis (36 mg) erzielte nach 72 Wochen eine signifikante Gewichtsabnahme von 22,9 lb (10,5%) gegenüber 5,1 lb (2,2%) im Placeboarm.
Wesentliche Erfolge umfassen A1C-Reduktionen von 1,3% bis 1,8% ausgehend von einem Ausgangswert von 8,1%, wobei 75% der Teilnehmenden einen A1C-Wert ≤6,5% erreichten. Das Medikament zeigte Verbesserungen kardiovaskulärer Risikofaktoren und eine Reduktion entzündlicher Marker um 50,6%. Das Sicherheitsprofil entsprach dem injizierbarer GLP-1-Präparate, mit überwiegend leichten bis mäßigen gastrointestinale Nebenwirkungen.
Auf Basis dieser Ergebnisse plant Lilly, weltweite Zulassungsanträge für die Zulassung von orforglipron als einmal täglich oral einzunehmende Behandlung einzureichen.
- Significant weight loss of 22.9 lbs (10.5%) achieved with highest dose vs 5.1 lbs (2.2%) with placebo
- Strong A1C reductions of 1.3% to 1.8% from baseline of 8.1%
- 75% of participants on highest dose achieved A1C ≤6.5%
- Meaningful improvements in cardiovascular risk factors and 50.6% reduction in inflammation markers
- Overall treatment discontinuation rates balanced across groups (19.1-22.3%)
- No hepatic safety signals observed
- Higher adverse events vs placebo: nausea (36.4% vs 8.4%), vomiting (23.1% vs 3.8%), diarrhea (27.4% vs 15.0%)
- Treatment discontinuation due to adverse events higher than placebo (10.6% vs 4.6%) for higher doses
Insights
Lilly's oral GLP-1 drug shows strong Phase 3 results with 10.5% weight loss and 1.8% A1C reduction, positioning it as potentially first-in-class oral obesity treatment.
Lilly's orforglipron Phase 3 ATTAIN-2 trial results represent a significant milestone in obesity treatment. The once-daily oral GLP-1 demonstrated 10.5% average weight reduction (22.9 lbs) at the highest dose versus 2.2% with placebo over 72 weeks in patients with obesity/overweight and type 2 diabetes - a population typically resistant to weight loss interventions.
Most impressive is the A1C reduction of 1.8% from baseline 8.1%, with 75% of high-dose participants achieving A1C ≤6.5%, effectively bringing glucose levels below the diabetes threshold. The drug also showed meaningful improvements in cardiovascular risk factors including non-HDL cholesterol, blood pressure, triglycerides, and inflammation (hsCRP reduced by 50.6%).
The safety profile mirrors injectable GLP-1s with primarily mild-to-moderate gastrointestinal effects. Treatment discontinuation rates were balanced across groups (19.1-22.3% for orforglipron vs. 20.0% placebo), though adverse event discontinuations were slightly higher with orforglipron (6.1-10.6% vs. 4.6% placebo). Notably, no hepatic safety signals emerged - a critical consideration for oral metabolic drugs.
With this final Phase 3 trial completed, Lilly now has the complete data package for global regulatory submissions. If approved, orforglipron would be the first oral GLP-1 specifically for obesity, potentially transforming treatment by eliminating injection barriers while maintaining efficacy comparable to injectable options. Its once-daily administration without food/water restrictions enhances its convenience profile in a market where patient adherence is crucial.
In ATTAIN-2, orforglipron met the primary and all key secondary endpoints, with compelling efficacy results and a safety profile consistent with injectable GLP-1 medicines
Participants with obesity or overweight and type 2 diabetes, a population with increased difficulties losing weight, lost an average of 22.9 lbs (
"Based on my experience leading clinical trials in obesity and diabetes, these data show the potential for orforglipron to offer an efficacy, safety, and tolerability profile consistent with the injectable GLP-1 class," said Louis J. Aronne, MD, FACP, DABOM, founder and Chair Emeritus of the American Board of Obesity Medicine, former president of The Obesity Society, Fellow of the American College of Physicians, and world-renowned obesity specialist. "Orforglipron could help health care providers expand treatment options for patients who prefer oral therapies without compromising clinical results."
In the ATTAIN-2 trial, orforglipron met the primary endpoint of superior body weight reduction compared to placebo. Participants taking the highest dose of orforglipron lost an average of 22.9 lbs (
Efficacy Estimand Results | ||||
Orforglipron 6 mg | Orforglipron 12 mg | Orforglipron 36 mg | Placebo | |
Primary Endpoint | ||||
Mean percent change in | -
(-5.5 kg; -12.1 lbs) | -
(-7.9 kg; -17.4 lbs) | -
(-10.4 kg; -22.9 lbs) | -
(-2.3 kg; -5.1 lbs) |
Key Secondary Endpoints | ||||
Percentage of participants achieving body weight reductions of ≥ | 23.9 % | 35.5 % | 50.1 % | 7.0 % |
Percentage of body weight reductions | 7.3 % | 17.7 % | 28.4 % | 1.9 % |
A1C reduction from avg. | -1.3 % | -1.6 % | -1.8 % | -0.1 % |
Percentage of participants achieving A1C < | 70.0 % | 78.0 % | 85.1 % | 23.0 % |
Percentage of participants achieving A1C ≤ | 56.2 % | 67.5 % | 75.0 % | 10.6 % |
iSuperiority test was adjusted for multiplicity with all three doses. iiSuperiority test was adjusted for multiplicity with the 12 mg and 36 mg doses. | ||||
For the treatment-regimen estimand, each dose of orforglipron led to statistically significant improvements across the primary and all key secondary endpoints, including:3,4
- Percent weight reduction: -
5.1% (-5.3 kg; -11.7 lbs; 6 mg), -7.0% (-7.2 kg; -15.9 lbs; 12 mg), -9.6% (-9.6 kg; -21.2 lbs; 36 mg), -2.5% (-2.7 kg; -6.0 lbs; placebo) - Percentage of participants achieving body weight reductions of ≥
10% :22.6% (6 mg),31.2% (12 mg),45.6% (36 mg),9.0% (placebo) - Percentage of participants achieving body weight reductions of ≥
15% :6.8% (6 mg),14.4% (12 mg),26.0% (36 mg),3.0% (placebo) - A1C reduction: -
1.2% (6 mg), -1.5% (12 mg), -1.7% (36 mg), -0.5% (placebo) - Percentage of participants achieving A1C <
7% :64.6% (6 mg),75.9% (12 mg),75.5% (36 mg),30.5% (placebo) - Percentage of participants achieving A1C ≤
6.5% :52.5% (6 mg),57.6% (12 mg),66.6% (36 mg),15.4% (placebo)
"The ATTAIN-2 results reinforce the potential for orforglipron, as a once-daily oral, to deliver meaningful weight loss and A1C reduction, consistent with similar landmark trials for injectable GLP-1s," said Kenneth Custer, Ph.D., Lilly executive vice president and president of Lilly Cardiometabolic Health. "With these positive data in hand, we are moving with urgency toward global regulatory submissions to potentially meet the needs of patients who are waiting. If approved, we are ready to offer a convenient, once-daily pill that can be scaled globally — removing barriers and redefining how obesity is treated around the world."
The overall safety profile of orforglipron in ATTAIN-2 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 (
Detailed ATTAIN-2 results will be presented at a future medical meeting and published in a peer-reviewed journal.
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.5 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.6 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-2 and ATTAIN clinical trial program
ATTAIN-2 (NCT05872620) 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 monotherapy with placebo in adults with obesity or overweight and type 2 diabetes. The trial randomized over 1,600 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.
Endnotes and References
- The efficacy estimand represents efficacy had all randomized participants remained on study intervention (with possible dose interruptions and/or dose modifications) for 72 weeks without initiating prohibited weight management treatments (and glycemic rescue therapy for glycemic endpoints only).
- American Diabetes Association. (n.d.). Understanding diabetes diagnosis. Diabetes Diagnosis & Tests | ADA. https://diabetes.org/about-diabetes/diagnosis
- The treatment-regimen estimand represents the estimated average treatment effect regardless of adherence to study intervention or initiation of prohibited weight management treatments (or glycemic rescue therapy for glycemic endpoints only).
- Superiority test was adjusted for multiplicity with all three doses except for the percentage of participants achieving body weight reduction of ≥
15% where multiplicity adjustment applied to the 12 mg and 36 mg doses. - 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. doi: 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 obesity or overweight, 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 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.
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.
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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