Tang W H Wilson, Maroo Anjli
Department of Cardiovascular Medicine, The Cleveland Clinic, Cleveland, OH 44195, USA.
Diabetes Obes Metab. 2007 Jul;9(4):447-54. doi: 10.1111/j.1463-1326.2006.00616.x.
PPARgamma agonists (or thiazolidinediones, TZD) are popular oral drugs for glycaemic control in patients with diabetes mellitus. However, side-effects of fluid retention, oedema and congestive heart failure have been reported in the literature as well as observed in clinical registries and trials. Concerns regarding the safety of TZD use in patients with underlying heart failure have been implicated by its propensity to cause fluid retention. There is relatively good documentation in the literature that TZDs do not produce adverse haemodynamic consequences. TZD-induced fluid retention is often sub-acute in nature, developed over weeks to months following initiation, and primarily located in the periphery. Drug withdrawal may lead to complete resolution of fluid retention. Current approval of TZD use in patients with mild (NYHA class I - II) and stable heart failure is supported by existing literature and clinical experience. There have been few reports of severe adverse consequences following drug withdrawal, and emerging data are suggesting potential benefits of TZDs in the diabetic population with or without underlying heart failure. Future research should therefore be directed at better understanding PPARgamma-related mechanisms of renal sodium retention and endothelial vascular permeability of the periphery, as well as development of newer compounds without this side-effect.
过氧化物酶体增殖物激活受体γ激动剂（或噻唑烷二酮类药物，TZD）是糖尿病患者控制血糖常用的口服药物。然而，文献中已报道其存在液体潴留、水肿和充血性心力衰竭等副作用，临床登记和试验中也有观察到。由于TZD有导致液体潴留的倾向，因此对于在有潜在心力衰竭的患者中使用TZD的安全性存在担忧。文献中有相对充分的记录表明TZD不会产生不良血流动力学后果。TZD引起的液体潴留通常具有亚急性性质，在开始用药后的数周或数月内出现，且主要位于外周。停药可能导致液体潴留完全消退。现有文献和临床经验支持目前对轻度（纽约心脏协会心功能分级I - II级）且病情稳定的心力衰竭患者使用TZD的批准。停药后出现严重不良后果的报道很少，新出现的数据表明TZD对有或无潜在心力衰竭的糖尿病患者可能有益。因此，未来的研究应致力于更好地理解与过氧化物酶体增殖物激活受体γ相关的肾钠潴留机制以及外周内皮血管通透性，同时研发无此副作用的新型化合物。
