Pioglitazone
Pioglitazone
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DOI：
10.2165/00003495-200060020-00009
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发表时间：
2000-08-01
期刊：
影响因子：
11.5
通讯作者：
Dunn, CJ
中科院分区：
文献类型：
--
作者：
Gillies, PS;Dunn, CJ
吡格列酮是一种口服胰岛素增敏噻唑烷二酮类药物，已开发用于治疗2型糖尿病。吡格列酮激活核过氧化物酶体增殖物激活受体-γ（PPAR-gamma），导致调节葡萄糖和脂质代谢的各种蛋白质的转录增加。这些蛋白质增强了胰岛素在肝脏和外周组织中的受体后作用，从而改善了血糖控制，而不增加胰岛素的内源性分泌。吡格列酮15至45 mg/天的单药治疗已显示可降低2型糖尿病患者的血液糖化血红蛋白（HbA（1c））水平。天至既存二甲双胍治疗，或吡格列酮15或30 mg/天至磺脲类药物、胰岛素或伏格列波糖治疗，在控制不佳的2型糖尿病患者中，吡格列酮可显著降低HbA（1c）和空腹血糖水平。对照临床研究。在临床研究中，所有年龄的成年患者均对该药物具有良好的耐受性。单药治疗报告了水肿，汇总数据显示，在磺脲类或胰岛素治疗基础上加用吡格列酮后，2 - 15%的患者发生低血糖。吡格列酮是噻唑烷二酮类药物的一员，用于治疗2型糖尿病，这是一种与多种代谢异常相关的疾病，包括胰岛素分泌受损和胰岛素抵抗。胰岛素抵抗导致外周组织对葡萄糖的利用减少和肝脏葡萄糖输出增加，是许多2型糖尿病患者的重要基础代谢异常。它被认为是代谢综合征（“X综合征”）的关键组成部分，其特征为血脂异常、高血压、动脉粥样硬化、向心性肥胖和葡萄糖代谢受损（由Saltiel和Olefskyl（[1]）以及Granberry和Fonseca（[2]）综述）。噻唑烷二酮类通过使肝脏和外周组织对胰岛素的作用敏感而起作用，从而改善胰岛素介导的葡萄糖处理。在本简介中讨论的所有动物和人体研究中，吡格列酮均经口给药。
Pioglitazone is an orally administered insulin sensitising thiazolidinedione agent that has been developed for the treatment of type 2 diabetes mellitus.Pioglitazone activates the nuclear peroxisome proliferator activated receptor-gamma (PPAR-gamma), which leads to the increased transcription of various proteins regulating glucose and lipid metabolism. These proteins amplify the post-receptor actions of insulin in the liver and peripheral tissues, which leads to improved glycaemic control with no increase in the endogenous secretion of insulin.In placebo-controlled clinical trials, monotherapy with pioglitazone 15 to 45 mg/day has been shown to decrease blood glycosylated haemoglobin (HbA(1c)) levels in patients with type 2 diabetes mellitus.The addition of pioglitazone 30 mg/day to preexisting therapy with metformin, or of pioglitazone 15 or 30 mg/day to sulphonylurea, insulin or voglibose therapy, has been shown to decrease HbA(1c) and fasting blood glucose levels significantly in patients with poorly controlled type 2 diabetes mellitus.Pioglitazone has also been associated with improvements in serum lipid profiles in randomised placebo-controlled clinical studies.The drug has been well tolerated by adult patients of all ages in clinical studies. Oedema has been reported with monotherapy, and pooled data have shown hypoglycaemia in 2 to 15% of patients after the addition of pioglitazone to sulphonylurea or insulin treatment. There have been no reports of hepatotoxicity.Pioglitazone is a member of the thiazolidine-dione group of drugs developed for the treatment of type 2 (non-insulin-dependent) diabetes mellitus, a disorder associated with a number of metabolic abnormalities that include impaired insulin secretion and insulin resistance. Insulin resistance leads to decreased glucose utilisation by the peripheral tissues and increased hepatic glucose output, and is an important underlying metabolic abnormality in many patients with type 2 diabetes mellitus. It is believed to be a key component of the metabolic syndrome ('syndrome X'), which is characterised by dyslipidaemia, hypertension, atherosclerosis, central obesity and impaired glucose metabolism (reviewed by Saltiel and Olefskyl([1]) and Granberry and Fonseca([2])). The thiazolidinediones act by sensitising the liver and peripheral tissues to the effects of insulin, which results in improved insulin-mediated glucose disposal.Pioglitazone was administered orally in all animal and human studies discussed in this profile.