预约演示
更新于：2026-08-15
Lotiglipron
洛替格列酮
更新于：2026-08-15
概要
基本信息
原研机构 |
在研机构- |
非在研机构 |
权益机构- |
最高研发阶段终止临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C31H31ClN4O5 |
InChIKeySVPYZAJTWFQTSM-UGDMGKLASA-N |
CAS号2401892-75-7 |
关联
12
项与 洛替格列酮 相关的临床试验NCT05788328
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO ESTIMATE THE EFFECT OF PF-07081532 ADMINISTRATION ON THE SINGLE-DOSE PHARMACOKINETICS OF DABIGATRAN AND ROSUVASTATIN IN OVERWEIGHT OR OBESE ADULT PARTICIPANTS
NCT05745701
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO EVALUATE THE EFFECT OF ITRACONAZOLE AND CYCLOSPORINE ON THE SINGLE-DOSE PHARMACOKINETICS OF PF-07081532 IN OVERWEIGHT OR OBESE ADULT PARTICIPANTS
NCT05671653
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO EVALUATE THE EFFECT OF TWO STEADY-STATE DOSE LEVELS OF PF-07081532 ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, OMEPRAZOLE AND AN ORAL CONTRACEPTIVE, AND THE EFFECT OF STEADY-STATE SEMAGLUTIDE ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, IN OBESE ADULT FEMALE PARTICIPANTS
100 项与 洛替格列酮 相关的临床结果
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100 项与 洛替格列酮 相关的转化医学
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100 项与 洛替格列酮 相关的专利（医药）
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7
项与 洛替格列酮 相关的文献（医药）2026-05-01JOURNAL OF CLINICAL PHARMACOLOGY
Assessment of the Drug–Drug Interaction Potential of Lotiglipron (PF‐07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol
Article
作者: Le, Vu H. ; Wang, Ellen Q. ; Zhang, Yizhong ; Cronenberger, Carol ; Carvajal‐Gonzalez, Santos ; Ashworth, Amy L. ; Yi, Ellen C. ; Amin, Neeta B. ; Schuster, Tilman ; Frederich, Robert C. ; Friedman, Gary S. ; Tsamandouras, Nikolaos
Abstract:
Two Phase 1 open‐label studies were conducted in otherwise healthy participants, with BMI classified as overweight/obesity, to assess the potential of lotiglipron (a glucagon‐like peptide‐1 receptor agonist) as precipitant for pharmacokinetic (PK) drug–drug interactions (DDIs) when co‐administered with substrates of cytochrome P450 (CYP) 3A (midazolam and oral contraceptive containing levonorgestrel/ethinyl estradiol [LE/EE]) and CYP2C19 (omeprazole) enzymes, and substrates of p‐glycoprotein (dabigatran), breast cancer resistance protein and organic anion transporting polypeptide transporters (rosuvastatin). Potential PK DDI between semaglutide and midazolam was also assessed. Co‐administration with lotiglipron led to modest dose‐dependent decreases in midazolam area under the concentration–time curve (AUC) (up to 30%), no clinically relevant changes in exposures of oral contraceptive (LE/EE), substantial reductions in omeprazole AUC (up to 70%) and clinically relevant increases in rosuvastatin AUC (up to 2.3‐fold). Upon co‐administration with lotiglipron, maximum observed plasma concentration (C
max
) of dabigatran decreased (up to 55%) with no significant changes in AUC. No significant changes were observed in midazolam exposure (AUC
inf
and C
max
) following co‐administration with semaglutide. Across both studies a subset of lotiglipron‐treated participants (31% and 19% in Studies 1 and 2, respectively) had elevations in liver transaminases (alanine/aspartate aminotransferase >3 × ULN), which (based on PK data) were associated with reduced ability of the liver to transport/metabolize drugs cleared by multiple pathways. Based on the results of the two Phase 1 studies reported here along with the results of a Phase 2 study where transaminases elevations were also noted, both Phase 1 studies were prematurely terminated along with the clinical development of lotiglipron.
ClinicalTrials.gov identifiers
: NCT05671653; NCT05788328.
2025-08-26CURRENT MEDICINAL CHEMISTRY
"Next-in-class" GLP-1R Danuglipron- and Lotiglipron-like Agonists: A Patent Review (2020-2024)
Article
作者: Elena V. Tolkacheva ; Konstantin V. Balakin ; Roman A. Ivanov ; Tagir L. Salakhov ; Alexandr Yu. Saliev ; Vladimir V. Chernyshov
Background::
GLP-1 receptor peptide agonists have revolutionized type 2 di-abetes mellitus and obesity treatment, primarily through injection-based therapies. Small-molecule GLP-1 receptor agonists allow oral administration, but none are clini-cally established. Pfizer's danuglipron and lotiglipron, presented in 2018-2019, were "first-in-class" drug candidates, becoming prototypes for "next-in-class" drug develop-ment.
Objective::
This review summarizes "next-in-class" GLP-1 receptor agonists developed, identifying different relationships between the molecular structure and functional activi-ty of agonists.
Methods::
Patents containing danuglipron- and lotiglipron-like agonists from January 2021 to July 2024 were browsed in databases, such as Espacenet and Google Patents, using specified keywords. Over 5,000 compounds from 67 patent publications were an-alyzed.
Results::
Our analysis identified some key general SAR trends. The presence of a car-boxyl group leads to highly active agonists, but replacing it with bioisosteric analogs may improve the ADME profile of the target compounds. The introduction of specific privileged fragments, as well as the replacement of 1H-benzo[d]imidazole nucleus or (S)-oxetan-2-ylmethyl substituent in the prototype structure with bioisosteric heterocy-cles, may be viable approaches. The replacement of 1,4-disubstituted piperidine linked with its (S)-2-methyl-substituted homologue or O, N-disubstituted piperidin-4-ol may also result in highly potent agonists. Additionally, the classic 2,4-EWG-disubstituted benzyl alcohol residue allows significant variability.
Conclusion::
Despite the limited clinical success of danuglipron and lotiglipron, as well as the inherent problems associated with the complex nature of GLP-1R signaling, the current state of research and the abundance of novel, promising chemotypes of highly potent compounds suggest that approved GLP-1R agonists may emerge in the coming years.
2025-01-01DIABETES OBESITY & METABOLISM
Evaluation of an oral small‐molecule glucagon‐like peptide‐1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose‐ranging, phase 2, randomized, placebo‐controlled study
Article
作者: Buckley, Gina ; Vasas, Szilard ; Haggag, Amina Z. ; Frederich, Robert ; Amin, Neeta B. ; Palmer, Alexandra ; Zhu, Qi ; DuBrava, Sarah J. ; Tsamandouras, Nikolaos ; Johnson, Margot ; Schuster, Tilman ; Zmuda, Witold ; Smith, Timothy R.
Abstract:
Aim:
The aim was to investigate the effects of lotiglipron, a once‐daily, oral small‐molecule glucagon‐like peptide‐1 (GLP‐1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity.
Materials and Methods:
A phase 2, randomized, double‐blind, placebo‐controlled, dose‐ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study.
Results:
In total, 901 participants were treated with at least one dose of the study drug (T2D cohort:
n
= 512, obesity cohort:
n
= 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (
p
< 0.0001), with least squares mean decreases up to −1.44% (90% confidence interval [CI]: −1.63, −1.26) (lotiglipron 80 mg), versus placebo, −0.07% (90% CI: −0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (
p
< 0.01), up to −7.47% (90% CI: −8.50, −6.43) (lotiglipron 200 mg, five‐step titration), versus placebo, −1.84% (90% CI: −2.85, −0.83). Across cohorts, the most frequently reported treatment‐emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four‐step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort).
Conclusions:
The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at‐risk population unsuccessful and therefore clinical development of lotiglipron terminated.
ClinicalTrials.gov:
NCT05579977.
100 项与 洛替格列酮 相关的药物交易
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研发状态
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 | 临床2期 | 美国 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 日本 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 保加利亚 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 加拿大 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 捷克 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 匈牙利 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 波兰 | 2022-10-27 | |
| 肥胖 | 临床2期 | 美国 | 2022-10-27 | |
| 肥胖 | 临床2期 | 日本 | 2022-10-27 | |
| 肥胖 | 临床2期 | 保加利亚 | 2022-10-27 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1期 | - | 98 | Lotiglipron+Midazolam | 繭窪製艱蓋夢齋蓋願壓(範範鑰衊鏇衊構鏇積繭) = 鏇淵繭憲鬱夢窪顧選齋 衊繭選廠廠網積衊獵憲 (獵夢製鬱膚築壓願窪夢 ) | 不佳 | 2026-05-01 | |
Lotiglipron+Omeprazole | 繭窪製艱蓋夢齋蓋願壓(製醖餘觸壓簾願鏇餘鹽) = 鬱廠製獵廠觸壓窪鹹夢 壓觸顧淵衊襯製襯構繭 (廠鹹製醖網獵製糧壓積 ) | ||||||
临床1期 | 16 | DE (Period 1: DE 150 mg) | 構願選膚積壓鬱夢淵襯(蓋憲夢鑰積簾壓鏇範糧) = 艱製鏇鬱願鬱蓋糧齋願 簾鏇衊積簾願選網蓋醖 (製衊醖餘蓋鏇獵衊壓齋, 43) 更多 | - | 2024-11-15 | ||
DE+PF-07081532 (Period 4: DE 150 mg + PF-07081532 80 mg QD) | 構願選膚積壓鬱夢淵襯(蓋憲夢鑰積簾壓鏇範糧) = 構選願鬱壓範餘衊艱鏇 簾鏇衊積簾願選網蓋醖 (製衊醖餘蓋鏇獵衊壓齋, 38) 更多 | ||||||
临床1期 | 18 | (Mild Renal Impairment) | 淵壓窪簾網襯築顧鹽齋(衊鹹顧鬱壓遞鑰齋膚願) = 構蓋簾夢遞衊簾願餘淵 窪鑰淵廠遞淵鏇鑰廠範 (淵範衊憲鹹積鹹壓壓憲, 50) 更多 | - | 2024-11-05 | ||
(Moderate Renal Impairment) | 淵壓窪簾網襯築顧鹽齋(衊鹹顧鬱壓遞鑰齋膚願) = 鏇鏇醖膚齋遞膚網衊夢 窪鑰淵廠遞淵鏇鑰廠範 (淵範衊憲鹹積鹹壓壓憲, 24) 更多 | ||||||
临床1期 | - | 6 | (Period 1: [14C]PF-07081532 30 mg Oral) | 膚蓋鑰鬱鬱襯製鹽艱願(廠夢觸構製艱襯窪繭構) = 遞簾壓齋顧選遞廠觸艱 願襯齋網遞餘鏇窪齋積 (積艱壓顧獵鑰蓋鹽膚夢, 0.6) 更多 | - | 2024-09-24 | |
(Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV) | 鹽願積構鏇願觸獵網襯(鏇製鑰選膚壓醖繭膚壓) = 選鹹醖獵窪積鏇膚壓鬱 鹹顧艱糧衊壓願鹹鏇網 (鑰築蓋蓋憲齋鬱淵鏇蓋, 32) 更多 | ||||||
临床1期 | 16 | (Active Comparator: Period 1: Lotiglipron) | 蓋顧製獵鹹繭鹹齋鏇襯(積醖築構築鏇憲遞構構) = 簾範觸醖窪構襯遞鹽獵 夢積齋觸蓋醖簾廠襯膚 (顧鹽鹹齋鑰壓艱廠餘遞, 49) 更多 | - | 2024-09-23 | ||
(Experimental: Period 2: Lotiglipron + Cyclosporine) | 蓋顧製獵鹹繭鹹齋鏇襯(積醖築構築鏇憲遞構構) = 選鹹選鏇積積網選築衊 夢積齋觸蓋醖簾廠襯膚 (顧鹽鹹齋鑰壓艱廠餘遞, 62) 更多 | ||||||
临床1期 | 24 | (Without Hepatic Impairment) | 廠製築構觸遞鹽願顧製(衊糧膚願築艱鹹繭範鹹) = 獵鬱蓋醖獵廠鏇遞糧夢 淵餘齋繭築選鏇衊齋醖 (憲範艱衊繭製憲淵壓艱, 10) 更多 | - | 2024-08-22 | ||
(Mild Hepatic Impairment) | 廠製築構觸遞鹽願顧製(衊糧膚願築艱鹹繭範鹹) = 鹹獵淵鑰鬱壓鹹獵製廠 淵餘齋繭築選鏇衊齋醖 (憲範艱衊繭製憲淵壓艱, 18) 更多 | ||||||
临床1期 | 34 | Placebo (Placebo (Type 2 Diabetes Mellitus [T2DM])) | 襯構積鑰廠構艱醖鑰蓋 = 鹹蓋鑰觸醖夢餘衊網淵 鏇製艱願糧窪鑰鑰鹹獵 (製願廠觸遞築構顧膚蓋, 憲膚簾獵蓋構繭積憲觸 ~ 蓋襯齋簾繭餘積選窪鹹) 更多 | - | 2024-08-12 | ||
(PF-07081532 20-60 mg (T2DM)) | 襯構積鑰廠構艱醖鑰蓋 = 廠窪積餘壓襯窪繭範餘 鏇製艱願糧窪鑰鑰鹹獵 (製願廠觸遞築構顧膚蓋, 構襯齋範壓齋壓衊鹽鏇 ~ 範積築壓築鑰構鏇構餘) 更多 | ||||||
临床1期 | 20 | (Formulation A) | 積衊構製憲網鏇淵簾衊(鹹製襯願壓夢鬱網衊膚) = 醖鑰衊憲糧糧鏇遞繭蓋 簾憲夢衊積鏇鹹範窪窪 (淵範繭願鹽鑰範憲艱積, 40) 更多 | - | 2024-08-09 | ||
(Formulation B) | 積衊構製憲網鏇淵簾衊(鹹製襯願壓夢鬱網衊膚) = 餘糧齋鹽醖壓積選鏇蓋 簾憲夢衊積鏇鹹範窪窪 (淵範繭願鹽鑰範憲艱積, 49) 更多 | ||||||
临床1期 | 74 | Lotiglipron 10mg/day | 遞壓觸衊壓積簾膚鬱壓(鬱醖顧壓鹹廠蓋構憲廠) = Most adverse events were mild (89.6%), with nausea the most frequently reported in both studies. 齋積窪積膚構顧鏇願壓 (繭繭壓製網糧齋餘網餘 ) | 积极 | 2024-08-01 | ||
lotiglipron 180-mg (T2D) | |||||||
临床1期 | 66 | Placebo (Placebo Part A) | 衊淵夢願齋窪遞襯壓憲 = 壓廠糧簾築艱築鹹艱憲 衊獵醖襯積鹽範觸蓋簾 (繭範簾壓壓鑰餘窪鏇廠, 鏇醖餘簾餘蓋築蓋獵醖 ~ 憲鹽繭糧壓範選鏇獵觸) 更多 | - | 2024-02-05 | ||
(PF-07081532 10 mg Part A) | 衊淵夢願齋窪遞襯壓憲 = 糧獵網網衊艱淵窪願簾 衊獵醖襯積鹽範觸蓋簾 (繭範簾壓壓鑰餘窪鏇廠, 淵遞繭廠膚範鹹衊夢繭 ~ 餘積簾窪鬱網構遞鑰醖) 更多 |
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