Department of Medicine, Rudolfstiftung Hospital, Vienna, Austria.
Int J Clin Pract. 2009 Jun;63(6):912-29. doi: 10.1111/j.1742-1241.2009.02025.x.
The thiazolidinediones pioglitazone and rosiglitazone have established efficacy in improving insulin sensitivity, glycaemic control, dyslipidaemia, hypertension and microalbuminuria in patients with type 2 diabetes. As specific agonists of peroxisome proliferator-activated receptor-gamma, thiazolidinediones have also demonstrated protective effects on a variety of atherosclerosis biomarkers and surrogate measures of cardiovascular disease.
This paper reviews the evidence for pleiotropic effects on a variety of non-traditional atherosclerotic risk factors.
Thiazolidinediones attenuate circulating levels of pro-inflammatory mediators in patients with type 2 diabetes, including C-reactive protein, interleukin-6, CD40L, monocyte chemoattractant protein-1 and metalloproteinase-9. These agents also increase levels of the vascular protective adipokine, adiponectin. The clinical significance of these findings is supported by evidence of improved endothelial dysfunction, reduced carotid intima media thickness and improvements in stenosis following coronary artery stent implantation in patients treated with thiazolidinediones. Limited data suggest that thiazolidinediones might also improve the circulating levels and functional activity of angiogenic endothelial progenitor cells, which independently predict the incidence of cardiovascular events and death. It should be noted that the US Food and Drug Administration and the European Medicines Agency have requested changes to the prescribing information for rosiglitazone to highlight the possibility of an increased risk with this agent in patients with ischaemic heart disease; on review, no such amendment was required for the pioglitazone prescribing information. Both agencies continue to suggest that the benefits of both thiazolidinediones outweight any possible detrimental effects. Further research remains to be conducted to elucidate the potentially differential vascular protective effects of thiazolidinediones. In the US, there are black box heart failure warnings for both agents.
In light of the established importance of reducing cardiovascular risk in patients with type 2 diabetes, current evidence continues to support the use of pioglitazone within multifactorial risk management strategies.
噻唑烷二酮类药物吡格列酮和罗格列酮已被证实能有效改善 2 型糖尿病患者的胰岛素敏感性、血糖控制、血脂异常、高血压和微量白蛋白尿。作为过氧化物酶体增殖物激活受体-γ的特异性激动剂，噻唑烷二酮类药物还显示出对多种动脉粥样硬化生物标志物和心血管疾病替代指标的保护作用。
本文综述了噻唑烷二酮类药物对多种非传统动脉粥样硬化危险因素的多效性作用的证据。
噻唑烷二酮类药物可降低 2 型糖尿病患者循环中促炎介质的水平，包括 C 反应蛋白、白细胞介素-6、CD40L、单核细胞趋化蛋白-1 和金属蛋白酶-9。这些药物还能增加血管保护性脂肪因子脂联素的水平。这些发现的临床意义得到了以下证据的支持：在接受噻唑烷二酮类药物治疗的患者中，内皮功能障碍得到改善，颈动脉内膜中层厚度减少，冠状动脉支架植入术后狭窄程度改善。有限的数据表明，噻唑烷二酮类药物也可能改善循环中血管生成内皮祖细胞的水平和功能活性，而这些细胞独立预测心血管事件和死亡的发生率。应当指出，美国食品和药物管理局和欧洲药品管理局已要求修改罗格列酮的处方信息，以强调该药物在缺血性心脏病患者中风险增加的可能性；经审查，吡格列酮的处方信息不需要进行此类修改。这两个机构仍然认为，这两种噻唑烷二酮类药物的益处超过任何可能的不利影响。需要进一步研究阐明噻唑烷二酮类药物潜在的不同血管保护作用。在美国，这两种药物都有心力衰竭的黑框警告。
鉴于降低 2 型糖尿病患者心血管风险的重要性，目前的证据仍然支持在多因素风险管理策略中使用吡格列酮。
