主要目的：以Novartis Singapore Pharmaceutical Manufacturing Pte. Ltd生产的那格列奈片(规格：120mgg，商品名：Starlix®)为参比制剂，以江苏德源药业股份有限公司生产的那格列奈片(规格：120mg)为受试制剂，来评价空腹及餐后条件下的生物等效性。次要目的：在研究过程中，通过不良事件发生率、实验室检验结果、生命体征和体格检查等的变化情况评估那格列奈片的安全性。

开始日期2018-06-20

申办/合作机构

江苏德源药业股份有限公司

CTR20180642 / Completed

那格列奈片在健康受试者中的单剂量、随机、开放性、交叉、正式、空腹及餐后生物等效性研究

以天方药业有限公司研制的那格列奈片为受试制剂，由Novartis生产的那格列奈片（商品名：STARLIX）为参比制剂，进行空腹/餐后状态下人体生物利用度与生物等效性试验，计算受试制剂的相对生物利用度，评价两种制剂的生物等效性，并评价受试制剂和参比制剂在健康受试者中的安全性。

开始日期2018-05-08

申办/合作机构

天方药业有限公司

100 项与 PPARγ x SUR1 相关的临床结果

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100 项与 PPARγ x SUR1 相关的转化医学

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0 项与 PPARγ x SUR1 相关的专利（医药）

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项与 PPARγ x SUR1 相关的文献（医药）

2024-10-01·Health Science Reports

Genetically Proxied Antidiabetic Drug Target and Primary Open‐Angle Glaucoma: A Mendelian Randomization Study

Article

作者: Tang, Kefu ; Chang, Weiteng ; Wang, Wenqiu ; Wu, Xi

ABSTRACTBackground and AimsObservational studies suggest that antidiabetic drugs may lower POAG risk; while the causal relationship remains unclear. Naturally occurring variation in genes encoding antidiabetics drug targets can be used as proxies to investigate long‐term therapeutic effect of these drugs on POAG risk.MethodsWe performed a two‐sample Mendelian randomization study to evaluate the potential effect of antidiabetic drug targets on POAG in Europeans and East Asians. To proxy antidiabetic drugs (ABCC8, PPARG, GLP1R, SLC5A2), we leveraged genetic variants located near or within drug target genes that were associated with HbA1c. The validity of our ancestry‐specific genetic instrument was checked with multipul positive control outcomes. Genetic summary statistics of POAG from the International Glaucoma Genetics Consortium, Global Biobank Meta‐analysis Initiative, and FinnGen consortia were analyzed for Europeans (38,164 cases and 1,576,179 controls) and East Asians (16,650 cases and 288,833 controls) separately. Inverse‐variance weighted random‐effects models were used as primary method.ResultsMR results provided consistent evidence of a protective effect of ABCC8 inhibition on POAG using data sets from IGG, GBMI, and FinnGen. Genetically predicted one‐standard deviation reduction in HbA1c from ABCC8 inhibition were significant associated with lower risk of POAG in Europeans (OR = 0.211, 95% CI: 0.133–0.333; p < 0.001) and East Asians (OR = 0.070, 95% CI: 0.011–0.459; p = 0.0056). The association between genetically predicted ABCC8 inhibition and risk of POAG was mainly mediated through intraocular pressure. No association was found for PPARG, SLC5A2, or GLP1R. Sensitivity analyses supported this observation.ConclusionsWe found a protective effect of genetically proxied ABCC8 inhibition on POAG risk in both Europeans and East Asians, highlighting ABCC8 as a promising candidate drug target for POAG, and mechanisms underlying the protective effect should also be investigated.

2024-09-01·eBioMedicine

Exploring antidiabetic drug targets as potential disease-modifying agents in osteoarthritis

Article

作者: Jin, Xinzhong ; Si, Shucheng ; Oo, Win Min ; Zhang, Yan ; Li, Guangyi ; Zhang, Yuqing ; Boer, Cindy G ; Duong, Vicky ; Cai, Qianying ; Hunter, David J ; Wei, Xiaojuan ; Gao, Youshui ; Zheng, Xianyou ; Fu, Kai ; Zhang, Changqing

BACKGROUNDOsteoarthritis is a leading cause of disability, and disease-modifying osteoarthritis drugs (DMOADs) could represent a pivotal advancement in treatment. Identifying the potential of antidiabetic medications as DMOADs could impact patient care significantly.METHODSWe designed a comprehensive analysis pipeline involving two-sample Mendelian Randomization (MR) (genetic proxies for antidiabetic drug targets), summary-based MR (SMR) (for mRNA), and colocalisation (for drug-target genes) to assess their causal relationship with 12 osteoarthritis phenotypes. Summary statistics from the largest genome-wide association meta-analysis (GWAS) of osteoarthritis and gene expression data from the eQTLGen consortium were utilised.FINDINGSSeven out of eight major types of clinical antidiabetic medications were identified, resulting in fourteen potential drug targets. Sulfonylurea targets ABCC8/KCNJ11 were associated with increased osteoarthritis risk at any site (odds ratio (OR): 2.07, 95% confidence interval (CI): 1.50-2.84, P < 3 × 10^-4), while PPARG, influenced by thiazolidinediones (TZDs), was associated with decreased risk of hand (OR: 0.61, 95% CI: 0.48-0.76, P < 3 × 10^-4), finger (OR: 0.50, 95% CI: 0.35-0.73, P < 3 × 10^-4), and thumb (OR: 0.49, 95% CI: 0.34-0.71, P < 3 × 10^-4) osteoarthritis. Metformin and GLP1-RA, targeting GPD1 and GLP1R respectively, were associated with reduced risk of knee and finger osteoarthritis. In the SMR analyses, gene expression of KCNJ11, GANAB, ABCA1, and GSTP1, targeted by antidiabetic drugs, was significantly linked to at least one osteoarthritis phenotype and was replicated across at least two gene expression datasets. Additionally, increased KCNJ11 expression was related to decreased osteoarthritis risk and co-localised with at least one osteoarthritis phenotype.INTERPRETATIONOur findings suggest a potential therapeutic role for antidiabetic drugs in treating osteoarthritis. The results indicate that certain antidiabetic drug targets may modify disease progression, with implications for developing targeted DMOADs.FUNDINGThis study was funded by the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (2022), the Shanghai Municipal Health Commission Health Industry Clinical Research Project (Grant No. 20224Y0139), Beijing Natural Science Foundation (Grant No. 7244458), and the Postdoctoral Fellowship Program (Grade C) of China Postdoctoral Science Foundation (Grant No. GZC20230130).

2024-03-01·European Journal of Medicinal Chemistry

A comprehensive review of small-molecule drugs for the treatment of type 2 diabetes mellitus: Synthetic approaches and clinical applications

Review

作者: Guo, Yuan-Yuan ; Gao, Hua ; Sun, Jin-Feng ; Zhang, Jing-Yi

Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder characterized by the body's resistance to insulin and inadequate production of insulin. Small molecule drugs to treat T2DM mainly control blood sugar levels by improving insulin sensitivity, increasing insulin secretion, or reducing liver glycogen production. With the deepening of research on the pathogenesis of diabetes, many drugs with new targets and mechanisms of action have been discovered. The targets of the drugs for T2DM are mainly dipeptidyl peptidase IV inhibitors (DPP4), sodium/glucose cotransporter 2 inhibitors (SGLT2), sulfonylurea receptor modulators (SUR), peroxisome proliferator-activated receptor γ agonists (PPARγ), etc. We are of the opinion that acquiring a comprehensive comprehension of the synthetic procedures employed in drug molecule production will serve as a source of inventive and pragmatic inspiration for the advancement of novel, more potent, and feasible synthetic methodologies. This review aims to outline the clinical applications and synthetic routes of some representative drugs to treat T2DM, which will drive the discovery of new, more effective T2DM drugs.