治疗2型糖尿病新靶点药物研究新进展

doi:10.12114/j.issn.1007-9572.2022.0115

中国全科医学 ›› 2022, Vol. 25 ›› Issue (20): 2551-2557.DOI: 10.12114/j.issn.1007-9572.2022.0115

所属专题：内分泌代谢性疾病最新文章合集；安全用药最新文章合集

治疗2型糖尿病新靶点药物研究新进展

张鹏翔¹, 曾霖¹, 孟璐¹, 黄倩¹, 王高祥², 刘德亮³^,^*()

¹518033　广东省深圳市，广州中医药大学第四临床医学院
²518033　广东省深圳市，南京中医药大学附属深圳市中医院
³518033　广东省深圳市中医院

收稿日期:2022-01-08 修回日期:2022-03-07 出版日期:2022-07-15 发布日期:2022-03-24
通讯作者: 刘德亮
张鹏翔，曾霖，孟璐，等.治疗2型糖尿病新靶点药物研究新进展[J].中国全科医学，2022，25（20）：2551-2557. [www.chinagp.net]
作者贡献：张鹏翔、曾霖负责文章的构思和设计、文献整理、撰写论文；孟璐、黄倩负责文献收集；王高祥负责论文修订；刘德亮负责文章的质量控制及审校，对文章整体负责、监督管理。
基金资助:
国家自然科学基金青年科学基金项目(81704002)

New Research Progress of the Novel Target Drugs for the Treatment of Type 2 Diabetes Mellitus

Pengxiang ZHANG¹, Lin ZENG¹, Lu MENG¹, Qian HUANG¹, Gaoxiang WANG², Deliang LIU³^,^*()

¹The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China
²Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen 518033, China
³Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China

Received:2022-01-08 Revised:2022-03-07 Published:2022-07-15 Online:2022-03-24
Contact: Deliang LIU
About author:
ZHANG P X, ZENG L, MENG L, et al. New research progress of the novel target drugs for the treatment of type 2 diabetes mellitus[J]. Chinese General Practice, 2022, 25 (20) : 2551-2557.

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摘要/Abstract

摘要： 目前的2型糖尿病（T2DM）临床治疗药物种类繁多，噻唑烷二酮类、磺酰脲类、双胍类及胰岛素等传统降糖药物的降糖机制与安全性存在差异。近年来各种关于治疗T2DM的新靶点药物层出不穷，葡萄糖激酶激动剂、多重肠促胰岛素激动剂、胰高血糖素受体拮抗剂等新靶点药物通过不同机制逐渐满足临床个性化的治疗要求。本文对当前T2DM新靶点药物的研究进展进行综述，并分析各类新靶点药物临床研究的优、劣势，以期为T2DM临床治疗提供基础指导。

关键词: 糖尿病，2型, 新靶点药物, 药物疗法, 综述

Abstract:

At present, there are many types of drugs for clinical treatment of type 2 diabetes mellitus (T2DM) , there are differences in the hypoglycemic mechanisms and safety of traditional hypoglycemic drugs such as thiazolidinediones, sulfonylureas, biguanides, and insulin. In recent years, an assortment of new target drugs has emerged in an endless stream.New target drugs such as glucokinase activators, multi-site receptor agonists for GLP-1, GIP and glucagon, glucagon receptor inhibitors have gradually assembled the necessities of personalized clinical treatment through different mechanisms. This article reviews the current research progress of new target drugs for T2DM, and analyzes the advantages and disadvantages of clinical research of various new target drugs, in order to provide basic guidance for the clinical treatment of T2DM.

Key words: Diabetes mellitus, type 2, New target drugs, Drug therapy, Review

张鹏翔,曾霖,孟璐,等. 治疗2型糖尿病新靶点药物研究新进展[J]. 中国全科医学, 2022, 25(20): 2551-2557. DOI: 10.12114/j.issn.1007-9572.2022.0115.
Pengxiang ZHANG,Lin ZENG,Lu MENG, et al. New Research Progress of the Novel Target Drugs for the Treatment of Type 2 Diabetes Mellitus[J]. Chinese General Practice, 2022, 25(20): 2551-2557. DOI: 10.12114/j.issn.1007-9572.2022.0115.

参考文献 78

[1]	KHAN M A B，HASHIM M J，KING J K，et al. Epidemiology of type 2 diabetes-global burden of disease and forecasted trends[J]. J Epidemiol Glob Health，2020，10（1）：107-111. DOI：10.2991/jegh.k.191028.001.
[2]	印成霞，许凤泉. 糖尿病类药物使用及不良反应的统计分析[J]. 中国实用医药，2020，15（1）：179-180. DOI：10.14163/j.cnki.11-5547/r.2020.01.086.
[3]	DING L C，FAN L，XU X D，et al. Identification of core genes and pathways in type 2 diabetes mellitus by bioinformatics analysis[J]. Mol Med Rep，2019，20（3）：2597-2608. DOI：10.3892/mmr.2019.10522.
[4]	FYFE M C，WHITE J R，TAYLOR A，et al. Glucokinase activator PSN-GK1 displays enhanced antihyperglycaemic and insulinotropic actions[J]. Diabetologia，2007，50（6）：1277-1287. DOI：10.1007/s00125-007-0646-8.
[5]	LI W，ZHANG X Q，SUN Y，et al. Recent clinical advances of glucokinase activators in the treatment of diabetes mellitus type 2[J]. Pharmazie，2020，75（6）：230-235. DOI：10.1691/ph.2020.0409.
[6]	CHEN L，ZHANGY，ZHUD L. 235-OR：dorzagliatin as a glucose sensitizer achieved sustained glycemic control with good safety profiles in drug-naive T2DM patients in a 52-week phase 3 monotherapy trial （SEED）[J]. Diabetes，2021，70（Supplement 1）. DOI：10.2337/db21-235-or.
[7]	CHEN L，ZHANGY，YANG W Y. 763-P：dorzagliatin add-on to metformin achieved sustained efficacy and good safety profiles in T2D patients in a 52-week phase 3 trial （DAWN）[J]. Diabetes，2021，70（Supplement 1）. DOI：10.2337/db21-763-p.
[8]	ZHU D L，GAN S L，LIU Y，et al. Dorzagliatin monotherapy in Chinese patients with type 2 diabetes：a dose-ranging，randomised，double-blind，placebo-controlled，phase 2 study[J]. Lancet Diabetes Endocrinol，2018，6（8）：627-636. DOI：10.1016/S2213-8587(18)30105-0.
[9]	ZHENG S，SHAO F，DING Y，et al. Safety，pharmacokinetics，and pharmacodynamics of globalagliatin，a glucokinase activator，in Chinese patients with type 2 diabetes mellitus：arandomized，phase ib，28-day ascending dose study[J]. Clin Drug Investig，2020，40（12）：1155-1166. DOI：10.1007/s40261-020-00971-x.
[10]	BONADONNA R C，HEISE T，ARBET-ENGELS C，et al. Piragliatin （RO4389620），a novel glucokinase activator，lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus：amechanistic study[J]. J Clin Endocrinol Metab，2010，95（11）：5028-5036. DOI：10.1210/jc.2010-1041.
[11]	SARABU R，BIZZARRO F T，CORBETT W L，et al. Discovery of piragliatin—first glucokinase activator studied in type 2 diabetic patients[J]. J Med Chem，2012，55（16）：7021-7036. DOI：10.1021/jm3008689.
[12]	ZHI J G，ZHAI S P，BOLDRIN M. Dose-dependent effect of piragliatin，a glucokinase activator，on the QT interval following short-term multiple doses in patients with type 2 diabetes mellitus[J]. Clin Pharmacol Drug Dev，2017，6（3）：258-265. DOI：10.1002/cpdd.289.
[13]	POITOUT V，LIN D C H. Modulating GPR40：therapeutic promise and potential in diabetes[J]. Drug Discov Today，2013，18（23/24）：1301-1308. DOI：10.1016/j.drudis.2013.09.003.
[14]	YAMADA H，YOSHIDA M，ITO K，et al. Potentiation of glucose-stimulated insulin secretion by the GPR40-PLC-TRPC pathway in pancreatic β-cells[J]. Sci Rep，2016，6：25912. DOI：10.1038/srep25912.
[15]	MENON V，LINCOFF A M，NICHOLLS S J，et al. Fasiglifam-induced liver injury in patients with type 2 diabetes：results of a randomized controlled cardiovascular outcomes safety trial[J]. Diabetes Care，2018，41（12）：2603-2609. DOI：10.2337/dc18-0755.
[16]	BAZYDLO-GUZENDA K，BUDA P，MACH M，et al. Evaluation of the hepatotoxicity of the novel GPR40 （FFAR1） agonist CPL207280 in the rat and monkey[J]. PLoS One，2021，16（9）：e0257477. DOI：10.1371/journal.pone.0257477.
[17]	BAZYDLO-GUZENDA K，BUDA P，MATLOKA M，et al. CPL207280，a novel G protein-coupled receptor 40/free fatty acid receptor 1-specific agonist，shows a favorable safety profile and exerts antidiabetic effects in type 2 diabetic animals[J]. Mol Pharmacol，2021，100（4）：335-347. DOI：10.1124/molpharm.121.000260.
[18]	KRUG A W，VADDADY P，RAILKAR R A，et al. Leveraging a clinical phase ib proof-of-concept study for the GPR40 agonist MK-8666 in patients with type 2 diabetes for model-informed phase Ⅱ dose selection[J]. ClinTranslSci，2017，10（5）：404-411. DOI：10.1111/cts.12479.
[19]	CAMPBELL J E，DRUCKER D J. Pharmacology，physiology，and mechanisms of incretin hormone action[J]. Cell Metab，2013，17（6）：819-837. DOI：10.1016/j.cmet.2013.04.008.
[20]	LUDVIK B，GIORGINO F，JÓDAR E，et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes （SURPASS-3）：a randomised，open-label，parallel-group，phase 3 trial[J]. Lancet，2021，398（10300）：583-598. DOI：10.1016/S0140-6736(21)01443-4.
[21]	TILLNER J，POSCH M G，WAGNER F，et al. A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899：results of randomized，placebo-controlled first-in-human and first-in-patient trials[J]. Diabetes Obes Metab，2019，21（1）：120-128. DOI：10.1111/dom.13494.
[22]	VISENTIN R，SCHIAVON M，GÖBEL B，et al. Dual glucagon-like peptide-1 receptor/glucagon receptor agonist SAR425899 improves beta-cell function in type 2 diabetes[J]. Diabetes Obes Metab，2020，22（4）：640-647. DOI：10.1111/dom.13939.
[23]	NAHRA R，WANG T，GADDE K M，et al. Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes：a 54-week randomized phase 2b study[J]. Diabetes Care，2021，44（6）：1433-1442. DOI：10.2337/dc20-2151.
[24]	ASANO M，SEKIKAWA A，KIM H，et al. Pharmacokinetics，safety，tolerability and efficacy of cotadutide，a glucagon-like peptide-1 and glucagon receptor dual agonist，in phase 1 and 2 trials in overweight or obese participants of Asian descent with or without type 2 diabetes[J]. Diabetes Obes Metab，2021，23（8）：1859-1867. DOI：10.1111/dom.14412.
[25]	DARBALAEI S，YULIANTIEE，DAIA T，et al. Evaluation of biased agonism mediated by dual agonists of the GLP-1 and glucagon receptors[J]. Biochem Pharmacol，2020，180：114150. DOI：10.1016/j.bcp.2020.114150.
[26]	WYNNE K，PARK A J，SMALL C J，et al. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans：a randomised controlled trial[J]. Int J Obes （Lond），2006，30（12）：1729-1736. DOI：10.1038/sj.ijo.0803344.
[27]	COHEN M A，ELLIS S M，LE ROUX C W，et al. Oxyntomodulin suppresses appetite and reduces food intake in humans[J]. J Clin Endocrinol Metab，2003，88（10）：4696-4701. DOI：10.1210/jc.2003-030421.
[28]	WYNNE K，PARK A J，SMALL C J，et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects：a double-blind，randomized，controlled trial[J]. Diabetes，2005，54（8）：2390-2395. DOI：10.2337/diabetes.54.8.2390.
[29]	SHANKAR S S，SHANKAR R R，MIXSON L A，et al. Native oxyntomodulin has significant glucoregulatory effects independent of weight loss in obese humans with and without type 2 diabetes[J]. Diabetes，2018，67（6）：1105-1112. DOI：10.2337/db17-1331.
[30]	ALEXIADOU K，TAN T M M. Gastrointestinal peptides as therapeutic targets to mitigate obesity and metabolic syndrome[J]. CurrDiabetes Rep，2020，20（7）：1-7. DOI：10.1007/s11892-020-01309-9.
[31]	YANG P Y，ZOU H F，AMSO Z，et al. New generation oxyntomodulin peptides with improved pharmacokinetic profiles exhibit weight reducing and anti-steatotic properties in mice[J]. Bioconjug Chem，2020，31（4）：1167-1176. DOI：10.1021/acs.bioconjchem.0c00093.
[32]	DING W X，WANG H Y，PENG L J，et al. Novel peptidic dual GLP-1/glucagon receptor agonist alleviates diabetes and diabetic complications in combination with low-intensity ultrasound[J]. Eur Rev Med Pharmacol Sci，2020，24（23）：12423-12436. DOI：10.26355/eurrev_202012_24038.
[33]	LAFFERTY R A，O'HARTE F P M，IRWIN N，et al. Proglucagon-derived peptides as therapeutics[J]. Front Endocrinol（Lausanne），2021，12：689678. DOI：10.3389/fendo.2021.689678.
[34]	KIM M K，CHEONG Y H，LEE S H，et al. A novel GPR119 agonist DA-1241 preserves pancreatic function via the suppression of ER stress and increased PDX1 expression[J]. Biomedecine Pharmacother，2021，144：112324. DOI：10.1016/j.biopha.2021.112324.
[35]	MATSUMOTO K，YOSHITOMI T，ISHIMOTO Y，et al. DS-8500a，an orally available G protein-coupled receptor 119 agonist，upregulates glucagon-like peptide-1 and enhances glucose-dependent insulin secretion and improves glucose homeostasis in type 2 diabetic rats[J]. J Pharmacol Exp Ther，2018，367（3）：509-517. DOI：10.1124/jpet.118.250019.
[36]	YAMADA Y，TERAUCHI Y，WATADA H，et al. Efficacy and safety of GPR119 agonist DS-8500a in Japanese patients with type 2 diabetes：a randomized，double-blind，placebo-controlled，12-week study[J]. AdvTher，2018，35（3）：367-381. DOI：10.1007/s12325-018-0668-2.
[37]	TERAUCHI Y，YAMADA Y，WATADA H，et al. Efficacy and safety of the G protein-coupled receptor 119 agonist DS-8500a in Japanese type 2 diabetes mellitus patients with inadequate glycemic control on sitagliptin：a phase 2 randomized placebo-controlled study[J]. J Diabetes Investig，2018，9（6）：1333-1341. DOI：10.1111/jdi.12846.
[38]	KATO M，FURUIE H，KAMIYAMA E，et al. Safety and pharmacokinetics of DS-8500a，a novel GPR119 agonist，after multiple oral doses in healthy Japanese males[J]. Clin Drug Investig，2018，38（6）：519-525. DOI：10.1007/s40261-018-0633-5.
[39]	RITTER K，BUNING C，HALLAND N，et al. G protein-coupled receptor 119 （GPR119） agonists for the treatment of diabetes：recent progress and prevailing challenges[J]. J Med Chem，2016，59（8）：3579-3592. DOI：10.1021/acs.jmedchem.5b01198.
[40]	KANG S U. GPR119 agonists：a promising approach for T2DM treatment? A SWOT analysis of GPR119[J]. Drug Discov Today，2013，18（23/24）：1309-1315. DOI：10.1016/j.drudis.2013.09.011.
[41]	ANSARULLAH，LU Y，HOLSTEIN M，et al. Stimulating β-cell regeneration by combining a GPR119 agonist with a DPP-IV inhibitor[J]. PLoS One，2013，8（1）：e53345. DOI：10.1371/journal.pone.0053345.
[42]	LI G，HUAN Y，YUAN B K，et al. Discovery of novel xanthine compounds targeting DPP-IV and GPR119 as anti-diabetic agents[J]. Eur J Med Chem，2016，124：103-116. DOI：10.1016/j.ejmech.2016.08.023.
[43]	HUAN Y，JIANG Q，LI G，et al. The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo[J]. Sci Rep，2017，7（1）：4351. DOI：10.1038/s41598-017-04633-5.
[44]	LI G，MENG B X，YUAN B K，et al. The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119[J]. Eur J Med Chem，2020，188：112017. DOI：10.1016/j.ejmech.2019.112017.
[45]	BOUHAJJA H，ABDELHEDI R，AMOURI A，et al. Potential role of liver enzyme levels as predictive markers of glucose metabolism disorders in a Tunisian population[J]. Can J Physiol Pharmacol，2018，96（11）：1171-1180. DOI：10.1139/cjpp-2017-0579.
[46]	SHIBABAW T，DESSIE G，MOLLA M D，et al. Assessment of liver marker enzymes and its association with type 2 diabetes mellitus in Northwest Ethiopia[J]. BMC Res Notes，2019，12（1）：707. DOI：10.1186/s13104-019-4742-x.
[47]	KAZIERAD D J，BERGMAN A，TAN B，et al. Effects of multiple ascending doses of the glucagon receptor antagonist PF-06291874 in patients with type 2 diabetes mellitus[J]. Diabetes Obes Metab，2016，18（8）：795-802. DOI：10.1111/dom.12672.
[48]	GUZMAN C B，ZHANG X M，LIU R，et al. Treatment with LY2409021，a glucagon receptor antagonist，increases liver fat in patients with type 2 diabetes[J]. Diabetes Obes Metab，2017，19（11）：1521-1528. DOI：10.1111/dom.12958.
[49]	KAZDA C M，FRIAS J，FOGA I，et al. Treatment with the glucagon receptor antagonist LY2409021 increases ambulatory blood pressure in patients with type 2 diabetes[J]. Diabetes Obes Metab，2017，19（8）：1071-1077. DOI：10.1111/dom.12904.
[50]	VAJDA E G，POTTER S C，FUJITAKI J M，et al. LGD-6972，a potent，orally-bioavailable，small molecule glucagon receptor antagonist for the treatment of type 2 diabetes[J]. Diabetes，2012，61：A252.
[51]	VAJDA E G，LOGAN D，LASSETER K，et al. Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type 2 diabetes mellitus[J]. Diabetes Obes Metab，2017，19（1）：24-32. DOI：10.1111/dom.12752.
[52]	PETTUS J H，D'ALESSIO D，FRIAS J P，et al. Efficacy and safety of the glucagon receptor antagonist RVT-1502 in type 2 diabetes uncontrolled on metformin monotherapy：a 12-week dose-ranging study[J]. Diabetes Care，2020，43（1）：161-168. DOI：10.2337/dc19-1328.
[53]	HÆDERSDAL S，LUND A，MAAGENSEN H，et al. The glucagon receptor antagonist LY2409021 has no effect on postprandial glucose in type 2 diabetes[J]. Eur J Endocrinol，2022，186（2）：207-221. DOI：10.1530/EJE-21-0865.
[54]	BENNETT C F，SWAYZE E E. RNA targeting therapeutics：molecular mechanisms of antisense oligonucleotides as a therapeutic platform[J]. Annu Rev Pharmacol Toxicol，2010，50：259-293. DOI：10.1146/annurev.pharmtox.010909.105654.
[55]	CROOKE S T，WITZTUM J L，BENNETT C F，et al. RNA-targeted therapeutics[J]. Cell Metab，2019，29（2）：501. DOI：10.1016/j.cmet.2019.01.001.
[56]	MORGAN E S，TAI L J，PHAM N C，et al. Antisense inhibition of glucagon receptor by IONIS-GCGRRximproves type 2 diabetes without increase in hepatic glycogen content in patients with type 2 diabetes on stable metformin therapy[J]. Diabetes Care，2019，42（4）：585-593. DOI：10.2337/dc18-1343.
[57]	JOHNSON T O，ERMOLIEFF J，JIROUSEK M R. Protein tyrosine phosphatase 1B inhibitors for diabetes[J]. NatRev Drug Discov，2002，1（9）：696-709. DOI：10.1038/nrd895.
[58]	DIGENIO A，PHAM N C，WATTS L M，et al. Antisense inhibition of protein tyrosine phosphatase 1B with IONIS-PTP-1B_Rx improves insulin sensitivity and reduces weight in overweight patients with type 2 diabetes[J]. Diabetes Care，2018，41（4）：807-814. DOI：10.2337/dc17-2132.
[59]	LUO J，HOU Y F，XIE M Y，et al. CYC31，A natural bromophenol PTP1B inhibitor，activates insulin signaling and improves long chain-fatty acid oxidation in C2C12 myotubes[J]. Mar Drugs，2020，18（5）：E267. DOI：10.3390/md18050267.
[60]	BRUDER-NASCIMENTOT，BUTLER B R，HERRENDJ，et al. Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension[J]. Pharmacol Res，2015，102：235-244. DOI：10.1016/j.phrs.2015.10.012.
[61]	GUZMÁN-ÁVILA R，FLORES-MORALES V，PAOLI P，et al. Ursolic acid derivatives as potential antidiabetic agents：in vitro，in vivo，and in silico studies[J]. Drug Dev Res，2018，79（2）：70-80. DOI：10.1002/ddr.21422.
[62]	LIN X L，LIU Y B，HU H J. Metabolic role of fibroblast growth factor 21 in liver，adipose and nervous system tissues[J]. Biomed Rep，2017，6（5）：495-502. DOI：10.3892/br.2017.890.
[63]	KHARITONENKOV A，SHIYANOVA T L，KOESTER A，et al. FGF-21 as a novel metabolic regulator[J]. J Clin Invest，2005，115（6）：1627-1635. DOI：10.1172/JCI²3606.
[64]	KHARITONENKOV A，ADAMS A C. Inventing new medicines：the FGF21 story[J]. Mol Metab，2014，3（3）：221-229. DOI：10.1016/j.molmet.2013.12.003.
[65]	GAICH G，CHIEN J Y，FU H D，et al. The effects of LY2405319，an FGF21 analog，in obese human subjects with type 2 diabetes[J]. Cell Metab，2013，18（3）：333-340. DOI：10.1016/j.cmet.2013.08.005.
[66]	ABDELMALEK M F，CHARLES E D，SANYAL A J，et al. The FALCON program：two phase 2b randomized，double-blind，placebo-controlled studies to assess the efficacy and safety of pegbelfermin in the treatment of patients with nonalcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis[J]. Contemp Clin Trials，2021，104：106335. DOI：10.1016/j.cct.2021.106335.
[67]	KIM A M，SOMAYAJI V R，DONG J Q，et al. Once-weekly administration of a long-acting fibroblast growth factor 21 analogue modulates lipids，bone turnover markers，blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non-human Primates[J]. Diabetes Obes Metab，2017，19（12）：1762-1772. DOI：10.1111/dom.13023.
[68]	TURNER T，CHEN X，ZAHNER M，et al. FGF21 increases water intake，urine output and blood pressure in rats[J]. PLoS One，2018，13（8）：e0202182. DOI：10.1371/journal.pone.0202182.
[69]	PAN D S，WANG W，LIU N S，et al. Chiglitazar preferentially regulates gene expression via configuration-restricted binding and phosphorylation inhibition of PPARγ[J]. PPAR Res，2017，2017：4313561. DOI：10.1155/2017/4313561.
[70]	DEEKS E D. Chiglitazar：first approval[J]. Drugs，2022，82（1）：87-92. DOI：10.1007/s40265-021-01648-1.
[71]	LI X J，YU J，WU M，et al. Pharmacokinetics and safety of chiglitazar，a peroxisome proliferator-activated receptor pan-agonist，in patients <65 and ≥65 years with type 2 diabetes[J]. Clin Pharmacol Drug Dev，2021，10（7）：789-796. DOI：10.1002/cpdd.893.
[72]	LI R，METCALFE M J，FERGUSON J E 3rd，et al. Effects of thiazolidinedione in patients with active bladder cancer[J]. BJU Int，2018，121（2）：244-251. DOI：10.1111/bju.14009.
[73]	ROUSSEL R，HADJADJ S，PASQUET B，et al. Thiazolidinedione use is not associated with worse cardiovascular outcomes：a study in 28，332 high risk patients with diabetes in routine clinical practice：brief title：Thiazolidinedione use and mortality[J]. Int J Cardiol，2013，167（4）：1380-1384. DOI：10.1016/j.ijcard.2012.04.019.
[74]	GOLTSMAN I，KHOURY E E，WINAVER J，et al. Does Thiazolidinedione therapy exacerbate fluid retention in congestive heart failure? [J]. Pharmacol Ther，2016，168：75-97. DOI：10.1016/j.pharmthera.2016.09.007.
[75]	KU Y H，CHO B J，KIM M J，et al. Rosiglitazone increases endothelial cell migration and vascular permeability through Akt phosphorylation[J]. BMC Pharmacol Toxicol，2017，18（1）：62. DOI：10.1186/s40360-017-0169-y.
[76]	FAROOQUI K J，MITHAL A，KERWEN A K，et al. Type 2 diabetes and bone fragility—an under-recognized association[J]. Diabetes Metab Syndr，2021，15（3）：927-935. DOI：10.1016/j.dsx.2021.04.017.
[77]	DEPAOLI A M，HIGGINS L S，HENRY R R，et al. Can a selective PPARγ modulator improve glycemic control in patients with type 2 diabetes with fewer side effects compared with pioglitazone? [J]. Diabetes Care，2014，37（7）：1918-1923. DOI：10.2337/dc13-2480.
[78]	DEFRONZO R A. Lilly lecture 1987. The triumvirate：beta-cell，muscle，liver. A collusion responsible for NIDDM[J]. Diabetes，1988，37（6）：667-687. DOI：10.2337/diab.37.6.667.

治疗2型糖尿病新靶点药物研究新进展

New Research Progress of the Novel Target Drugs for the Treatment of Type 2 Diabetes Mellitus

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