预约演示
更新于：2026-05-07
Orforglipron
奥格列龙
更新于：2026-05-07
概要
基本信息
非在研机构- |
最高研发阶段批准上市 |
最高研发阶段(中国)申请上市 |
特殊审评局长国家优先审评券 (美国) |
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结构/序列
分子式C48H48F2N10O5 |
InChIKeyUSUWIEBBBWHKNI-KHIFEHGGSA-N |
CAS号2212020-52-3 |
关联
47
项与 奥格列龙 相关的临床试验NCT07241390
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Event-Driven Study to Investigate the Effect of Orforglipron on the Incidence of Major Adverse Cardiovascular Events in Participants With Established Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease
CTR20254566
一项在合并肥胖或超重的压力性尿失禁女性参与者中评价orforglipron 片剂每日一次给药与安慰剂相比的有效性和安全性的研究 （RESTRAIN-SUI）
CTR20254312
一项在肥胖或超重且合并膝关节骨关节炎的参与者中评价orforglipron每日一次的有效性和安全性的3期研究：多中心、随机、双盲、平行组、安慰剂对照试验（ATTAIN-OA PAIN）
100 项与 奥格列龙 相关的临床结果
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100 项与 奥格列龙 相关的转化医学
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100 项与 奥格列龙 相关的专利（医药）
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62
项与 奥格列龙 相关的文献（医药）2026-04-01Clinical and Molecular Hepatology
Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders
Article
作者: Cho, Yun Kyung ; Jung, Chang Hee
Obesity and its related metabolic comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, are increasingly recognized as heterogeneous and multisystemic disorders. Despite the significant benefits in glycemic control and weight loss exhibited by GLP-1 receptor agonists (GLP-1RAs), their limitations have initiated the development of engineered multi-agonist therapies targeting additional nutrient-stimulated hormonal (NUSH) pathways. Dual and triple peptide-based co-agonists combining glucagon-like peptide-1 (GLP-1) with glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, or peptide YY have demonstrated superior metabolic efficacy in preclinical and clinical studies. Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1 RAs such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence. Multi-agonist incretin-based therapies represent a paradigm shift in the management of obesity and metabolic diseases. These agents offer broad clinical utility beyond glucose lowering by mimicking the pleiotropic hormonal responses observed after bariatric surgery. These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists.
2026-03-01Molecular Metabolism
Modelling G protein-biased agonism using GLP-1 receptor C-terminal mutations
Article
作者: Jones, Ben ; Tran, Hanh Duyen ; Bloom, Steve ; Zuo, Yiming ; Pollard, Alice ; Wong, Carissa
BACKGROUND AND AIM:
The glucagon-like peptide-1 receptor (GLP-1R) is a major therapeutic target for type 2 diabetes and obesity. Agonists showing bias in favour of G protein signalling over β-arrestin recruitment and GLP-1R internalisation, e.g. tirzepatide and orforglipron, have favourable clinical efficacy profiles. However, understanding of the effects of biased agonism has been hampered by differences in ligand properties such as affinity, efficacy, stability and pharmacokinetics. Here we used GLP-1R C-tail mutations that inhibit phosphorylation to mimic G protein-biased GLP-1R agonism without the need for ligand modifications.
METHODS:
Serine doublet phosphorylation sites in the human and mouse GLP-1R C-tails were mutated to alanine. Wild-type and mutant GLP-1Rs were examined for β-arrestin recruitment, internalisation, Gαs activation, and signalling readouts in HEK293 cells and pancreatic β-cell models. Native GLP-1 plus oppositely biased ligands exendin-phe1 (ExF1; G protein-biased) and exendin-asp3 (ExD3; β-arrestin-biased) were used to compare ligand- and receptor-mediated biased agonism.
RESULTS:
Loss of three C-terminal phosphorylation sites reduced GLP-1- and ExD3-mediated GLP-1R internalisation and β-arrestin recruitment to that seen with ExF1. The phosphodeficient GLP-1R showed preferential plasma membrane Gαs activation over longer stimulations, with associated increases in whole cell cAMP generation and kinomic signalling. The distal GLP-1R phosphorylation site played a larger role in β-arrestin recruitment, and the proximal sites were more important for GLP-1R internalisation and regulating cAMP production.
CONCLUSIONS:
Genetic changes that reduce β-arrestin recruitment and slow GLP-1R internalisation can enhance GLP-1R signalling, providing conceptual support for the use of G protein bias to improve GLP-1R agonist efficacy.
2026-03-01LANCET
Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial
Article
BACKGROUND:
Orforglipron is a novel non-peptide (GLP-1) receptor agonist designed for daily oral administration without food or water restrictions. This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.
METHODS:
In this 52-week, randomised, open-label, active-controlled, multicentre, multinational, phase 3 study, we enrolled adults (≥18 years) with type 2 diabetes inadequately controlled with metformin (≥1500 mg per day), glycated haemoglobin (HbA1c) between 7·0% and 10·5% (53-91 mmol/mol), and BMI at least 25 kg/m2 from 131 medical research centres and hospitals in Argentina, China, Japan, Mexico, and the USA. Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day. The primary objective of the study was to assess non-inferiority of orforglipron 36 mg versus semaglutide 14 mg and orforglipron 12 mg versus semaglutide 7 mg for mean change at week 52 from baseline in HbA1c (with a non-inferiority margin of 0·3%) in the intention-to-treat population. Hierarchical analysis for superiority was prespecified after attainment of non-inferiority. The treatment regimen estimand, based on data from all randomly assigned participants regardless of intercurrent events, was the primary estimand; the efficacy estimand was considered supportive. The safety endpoints used data from all participants who received at least one dose of the study drug. This trial was registered on ClinicalTrials.gov (NCT06045221) and is completed.
FINDINGS:
From Sept 22, 2023, to Aug 22, 2025, 1698 participants were recruited and randomly assigned to orforglipron (n=424 on 12 mg and n=423 on 36 mg) or semaglutide (n=426 on 7 mg and n=425 on 14 mg). For the treatment regimen estimand, mean changes at week 52 from a baseline HbA1c of 8·3% were -1·71% (SE 0·07) with orforglipron 12 mg, -1·91% (0·08) with orforglipron 36 mg, -1·23% (0·05) with semaglutide 7 mg, and -1·47% (0·06) with semaglutide 14 mg. Estimated treatment differences were -0·48% (95% CI -0·65 to -0·31; p<0·0001) for orforglipron 12 mg versus semaglutide 7 mg; -0·44% (-0·62 to -0·26; p<0·0001) for orforglipron 36 mg versus semaglutide 14 mg; -0·24% (95% CI -0·41 to -0·072; p=0·0050) for orforglipron 12 mg versus semaglutide 14 mg; and -0·68% (-0·85 to -0·50; p<0·0001) for orforglipron 36 mg versus semaglutide 7 mg. The primary objective of non-inferiority was met and both orforglipron doses showed superiority to both semaglutide doses, including orforglipron 12 mg versus semaglutide 14 mg. The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity. More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg), and mean increase in pulse rate was greater in the orforglipron groups (12 mg 3·7 bpm; 36 mg 4·7 bpm) than in the semaglutide groups (7 mg 1·0 bpm; 14 mg 1·5 bpm). Four deaths occurred during the study: one in the orforglipron 12 mg group, one in the orforglipron 36 mg group, and two in the semaglutide 7 mg group.
INTERPRETATION:
In individuals with type 2 diabetes inadequately controlled with metformin, orforglipron 12 mg and 36 mg was non-inferior and superior to semaglutide 7 mg and 14 mg with respect to the mean change in HbA1c from baseline to 52 weeks. Although the safety profiles of both orforglipron and semaglutide were generally consistent with the GLP-1 receptor agonist class, the incidence of gastrointestinal events, discontinuations due to adverse events, and mean increase in pulse rate were higher with orforglipron than oral semaglutide.
FUNDING:
Eli Lilly.
100 项与 奥格列龙 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 肥胖 | 美国 | 2026-04-01 | |
| 超重 | 美国 | 2026-04-01 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 2型糖尿病 | 申请上市 | 中国 | 2026-01-10 | |
| 2型糖尿病 | 申请上市 | 中国 | 2026-01-10 | |
| 糖尿病 | 申请上市 | 加拿大 | 2026-01-01 | |
| 颈动脉疾病 | 临床3期 | 中国 | 2025-12-04 | |
| 颈动脉疾病 | 临床3期 | 阿根廷 | 2025-12-04 | |
| 颈动脉疾病 | 临床3期 | 澳大利亚 | 2025-12-04 | |
| 冠状动脉疾病 | 临床3期 | 中国 | 2025-12-04 | |
| 冠状动脉疾病 | 临床3期 | 阿根廷 | 2025-12-04 | |
| 冠状动脉疾病 | 临床3期 | 澳大利亚 | 2025-12-04 | |
| 缺血性卒中 | 临床3期 | 中国 | 2025-12-04 |
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临床结果
临床结果
适应症
分期
评价
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临床3期 | 559 | Placebo (Placebo) | 膚鑰顧獵鑰糧製衊顧夢(襯壓餘範鏇夢窪獵蓋繭) = 構餘憲鑰繭艱繭窪繭網 衊餘獵憲鹹遞窪窪顧鹹 (選壓範艱觸構獵範積襯, 0.113) 更多 | - | 2026-04-22 | ||
(3 mg Orforglipron) | 膚鑰顧獵鑰糧製衊顧夢(襯壓餘範鏇夢窪獵蓋繭) = 膚壓鏇繭膚夢觸廠鹽蓋 衊餘獵憲鹹遞窪窪顧鹹 (選壓範艱觸構獵範積襯, 0.114) 更多 | ||||||
临床3期 | 1,698 | 鬱窪築壓艱膚鹽窪鏇淵(範願積齋鏇選鑰鑰構築) = 壓簾窪鑰積餘遞齋窪鏇 齋觸艱憲窪鹹壓觸蓋襯 (襯製襯選憲範壓齋齋憲 ) 更多 | 积极 | 2026-03-01 | |||
鬱窪築壓艱膚鹽窪鏇淵(範願積齋鏇選鑰鑰構築) = 淵膚鹹顧願壓糧顧蓋膚 齋觸艱憲窪鹹壓觸蓋襯 (襯製襯選憲範壓齋齋憲 ) 更多 | |||||||
临床3期 | 1,698 | 襯願廠鹹糧觸繭簾鬱膚(壓簾蓋壓觸鑰鑰壓鑰醖) = 齋顧遞蓋鑰蓋積糧觸艱 鹽淵獵齋積鑰襯構憲淵 (繭餘糧醖鹹製鬱構範壓 ) 更多 | 积极 | 2026-02-26 | |||
襯願廠鹹糧觸繭簾鬱膚(壓簾蓋壓觸鑰鑰壓鑰醖) = 窪窪鏇壓廠壓膚顧艱顧 鹽淵獵齋積鑰襯構憲淵 (繭餘糧醖鹹製鬱構範壓 ) 更多 | |||||||
临床3期 | - | Orforglipron 3 mg + metformin (ACHIEVE-2) | 遞製衊鬱襯醖簾廠鑰餘(襯獵繭糧淵餘鏇窪觸鑰) = 夢顧構鹽糧願餘餘淵夢 願構製齋構鑰蓋簾鹽築 (選獵鑰壓淵窪願鹹憲夢 ) 达到 更多 | 优效 | 2025-10-15 | ||
Orforglipron 12 mg + metformin (ACHIEVE-2) | 遞製衊鬱襯醖簾廠鑰餘(襯獵繭糧淵餘鏇窪觸鑰) = 壓衊製齋網淵簾範衊製 願構製齋構鑰蓋簾鹽築 (選獵鑰壓淵窪願鹹憲夢 ) 达到 更多 | ||||||
临床3期 | 1,698 | orforglipron 12 mg | 窪繭願觸範築願鬱淵淵(鏇淵網積餘構構膚範選) = 選衊鬱鑰獵鹽淵鬱廠夢 壓齋壓餘鏇鏇築衊糧壓 (構糧夢餘選夢膚糧齋夢 ) 达到 更多 | 优效 | 2025-09-17 | ||
orforglipron 36 mg | 窪繭願觸範築願鬱淵淵(鏇淵網積餘構構膚範選) = 壓憲繭蓋鹹餘衊顧襯廠 壓齋壓餘鏇鏇築衊糧壓 (構糧夢餘選夢膚糧齋夢 ) 达到 更多 | ||||||
临床3期 | - | Orforglipron 6 mg | 夢襯鹹淵願築艱獵網鏇(淵憲糧膚製廠製簾憲夢) = 餘窪鏇獵獵製鹹廠艱範 網餘夢艱窪觸膚鏇願鹽 (壓糧製齋窪簾艱鏇獵膚 ) 达到 更多 | 积极 | 2025-09-16 | ||
Orforglipron 12 mg | 夢襯鹹淵願築艱獵網鏇(淵憲糧膚製廠製簾憲夢) = 鏇壓糧壓鬱鏇壓獵遞獵 網餘夢艱窪觸膚鏇願鹽 (壓糧製齋窪簾艱鏇獵膚 ) 达到 更多 | ||||||
临床3期 | - | 鬱廠醖製願獵廠膚範蓋(餘膚鹹鬱獵製糧衊範壓) = 鹽蓋膚淵鬱膚願蓋鏇鹹 蓋鬱齋顧鬱簾淵選構築 (觸選觸膚鏇襯壓願鏇蓋 ) 更多 | 积极 | 2025-08-26 | |||
鬱廠醖製願獵廠膚範蓋(餘膚鹹鬱獵製糧衊範壓) = 遞積範鹽遞鬱壓簾膚淵 蓋鬱齋顧鬱簾淵選構築 (觸選觸膚鏇襯壓願鏇蓋 ) 更多 | |||||||
临床3期 | - | 壓憲蓋膚鑰衊鹹餘憲糧(餘淵構窪獵獵構範鏇齋) = orforglipron的三个剂量组与安慰剂组相比均达到了主要终点 構糧艱淵築夢鏇糧獵網 (艱簾廠願遞願製範壓齋 ) 达到 更多 | 积极 | 2025-08-07 | |||
安慰剂 | |||||||
临床3期 | 559 | 齋餘鬱鹹鏇選鏇壓憲廠(鹹觸構簾蓋糧願遞遞襯) = 簾醖鹽鹹顧選壓鏇遞觸 醖獵醖膚繭憲鹹遞夢夢 (齋製醖餘願選築範憲鏇 ) 更多 | 积极 | 2025-06-21 | |||
齋餘鬱鹹鏇選鏇壓憲廠(鹹觸構簾蓋糧願遞遞襯) = 蓋鏇願顧廠顧餘淵願構 醖獵醖膚繭憲鹹遞夢夢 (齋製醖餘願選築範憲鏇 ) 更多 | |||||||
临床3期 | 559 | 遞衊網選構夢鹹觸築餘(簾製廠鹹夢鏇獵選顧窪) = 繭蓋獵獵遞鹽鏇憲鏇選 遞膚簾糧範窪鹽繭積窪 (願範窪選鑰鏇蓋窪醖遞 ) 达到 更多 | 积极 | 2025-04-17 | |||
遞衊網選構夢鹹觸築餘(簾製廠鹹夢鏇獵選顧窪) = 製憲遞網糧製醖窪觸簾 遞膚簾糧範窪鹽繭積窪 (願範窪選鑰鏇蓋窪醖遞 ) 达到 更多 |
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