临床试验:ADOPT和CHICAGO

2006年11月和12月发表了两项关于噻唑烷二酮(TZDs)的重要研究，TZDs是一类胰岛素增敏剂。目前可用的两种tzd是罗格列酮(文迪雅)和吡格列酮(爱可拓)。虽然将一种药物的研究结果应用于另一种药物是不正确的，但总的来说，两种tzd似乎具有相同的作用机制和效果。ADOPT试验是一项为期5年的研究，包括4,360名新诊断为2型糖尿病的成年人。参与者被随机分配或分成不同的组，接受二甲双胍、文迪雅(罗格列酮)或格列本脲(一种磺酰脲)。5年后，文迪雅组有40%的A1c <7%，而二甲双胍组为36%，格列本脲组为26%。这表明格列本脲的使用寿命不如文迪雅。服用文迪雅的患者A1c <7%的时间最长(60个月)，其次是二甲双胍(45个月)和格列本脲(33个月)。因此，罗格列酮比其他两种药物对糖尿病的控制更稳定。然而，文迪雅也导致体重显著增加。 Patients on the TZD gained 4.8 kg (10.5 lb) over five years, while those on metformin lost 2.9 kg (6.4 lb) and those on glyburide gained 1.6 kg (3.5 lb). Weight gain is clearly undesirable, and in previous studies Avandia has been linked to another cardiovascular complication, congestive heart failure, although in ADOPT, there was no difference shown. The CHICAGO study was a 72-week trial that included 462 adults with type 2 diabetes. The participants received either Actos (pioglitazone) or glimepiride, a sulfonylurea, to lower their fasting plasma glucose to <140 mg/dL (<7.8 mmol/L). The study was designed to look at the drugs' effect on a commonly used marker of atherosclerosis (plaque on the arteries) called carotid intima-media thickness (CIMT). Increases in CIMT are associated with higher risk for cardiovascular disease. At the end of the study, mean CIMT decreased by 0.001 mm in the Avandia group but increased by 0.012 mm in the glimepiride group. If we accept that CIMT is a valid surrogate measure of cardiovascular risk, then these results are highly favorable for Avandia. However, the study was not big enough to measure cardiovascular risk directly, so we don't actually know if risk was reduced. It's possible that Avandia improves CIMT but does not affect the more important endpoint: cardiovascular disease. Still, the TZD did produce more sustained improvements in A1c than glimepiride and raised levels of HDL (good cholesterol) while glimepiride did not.

底线:与二甲双胍和磺酰脲类药物相比，tzd能使糖化血红蛋白水平持续下降，但会导致体重显著增加，而且价格更贵。对它们有利的是，它们比磺酰脲类药物对血管系统更有益，可能降低心血管疾病的风险。磺酰脲类药物并不是口服降糖药的好选择，因为它们会导致体重增加，而且对血糖没有持续的好处。总的来说，单药治疗并不能很好地保持患者的目标，所以最大的收获是联合治疗对2型糖尿病至关重要。

(Kahn S.等。罗格列酮、二甲双胍或格列本脲单药治疗的血糖持久性NEJM。2006年12月7日。355(23): 2427 - 2443。Mazzone T.等。吡格列酮与格列美脲对2型糖尿病患者颈动脉内膜-中膜厚度的影响《美国医学协会杂志》上。2006年12月6日。296(21): 2572 - 2581。)