Wolffenbuttel B H, Sels J P, Huijberts M S
Dept. of Endocrinology & Metabolism, University Hospital Maastricht, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands.
Expert Opin Pharmacother. 2001 Mar;2(3):467-78. doi: 10.1517/14656566.2.3.467.
Type 2 diabetes mellitus is characterised by impaired insulin secretion, diminished peripheral insulin action and increased hepatic glucose production. Clinical trials have indicated that near-normal glucose control may reduce the risk for microvascular and - to a lesser extent - macrovascular complications in Type 2 diabetic patients. Thiazolidinediones improve insulin action by activating a nuclear receptor, PPARgamma. Therefore, these drugs are often referred to as 'insulin sensitisers'. Rosiglitazone is the second compound of this group. Clinical studies with rosiglitazone have shown that it is effective in lowering blood glucose levels in Type 2 diabetic patients treated with either diet alone, sulphonylurea or metformin. Preliminary studies suggest that rosiglitazone also improves glycaemic control in insulin-treated patients while even slightly decreasing insulin dose. The magnitude of the effects is, however, moderate. In diet-treated patients, the reduction of HbA1c levels amounted on average 0.5 - 1.5% and addition to existing sulphonylurea therapy decreased HbA1c by 1.0 - 1.2%. The clinical relevance of additional beneficial effects, i.e., on blood pressure and microalbuminuria, needs to be determined further. Rosiglitazone does not cause hypoglycaemia or gastrointestinal side effects. There is however some concern related to fluid retention, which seems to be an effect of all PPARgamma agonists. In patients treated with rosiglitazone, no severe hepatotoxic side effects have been noticed until now. In the treatment of our patients with Type 2 diabetes, drugs like rosiglitazone which directly reduce insulin resistance are very welcome but more data on its combined use with insulin are needed. Additional studies will also explore its long-term effects in sparing beta-cell function and reducing diabetes-related complications and atherosclerosis.
2型糖尿病的特征是胰岛素分泌受损、外周胰岛素作用减弱以及肝葡萄糖生成增加。临床试验表明，接近正常的血糖控制可能会降低2型糖尿病患者发生微血管并发症以及在较小程度上发生大血管并发症的风险。噻唑烷二酮类药物通过激活核受体PPARγ来改善胰岛素作用。因此，这些药物常被称为“胰岛素增敏剂”。罗格列酮是该类药物中的第二个化合物。对罗格列酮的临床研究表明，它对仅接受饮食治疗、磺脲类药物治疗或二甲双胍治疗的2型糖尿病患者降低血糖水平有效。初步研究表明，罗格列酮还能改善接受胰岛素治疗患者的血糖控制，同时甚至能略微降低胰岛素剂量。然而，其效果的程度是中等的。在接受饮食治疗的患者中，糖化血红蛋白（HbA1c）水平平均降低0.5 - 1.5%，在现有磺脲类药物治疗基础上加用罗格列酮可使HbA1c降低1.0 - 1.2%。其额外有益作用（即对血压和微量白蛋白尿的作用）的临床相关性还需要进一步确定。罗格列酮不会引起低血糖或胃肠道副作用。然而，有人担心其与液体潴留有关，这似乎是所有PPARγ激动剂的一个作用。在用罗格列酮治疗的患者中，到目前为止尚未发现严重的肝毒性副作用。在我们对2型糖尿病患者的治疗中，像罗格列酮这样能直接降低胰岛素抵抗的药物非常受欢迎，但还需要更多关于其与胰岛素联合使用的数据。进一步的研究还将探讨其在保护β细胞功能以及减少糖尿病相关并发症和动脉粥样硬化方面的长期作用。
