目的:糖尿病和血脂异常是导致死亡和发病的主要原因。根据国际准则,他汀类药物是糖尿病和/或血脂异常患者治疗的基石.然而,他汀类药物和抗糖尿病药物具有相反的药理作用,因为他汀类药物,特别是阿托伐他汀和瑞舒伐他汀,损害葡萄糖稳态,增加新发糖尿病的风险,而抗糖尿病药物改善血糖稳态。这项研究的目的是研究阿托伐他汀的作用,瑞舒伐他汀,和匹伐他汀对2型糖尿病(T2DM)和血脂异常患者在降糖药物稳定治疗期间的血糖稳态。
方法:这项研究是作为试点进行的,prospective,随机化,开放标签,具有盲法终点(PROBE)研究的平行组。在招募的180名T2DM和血脂异常患者中,131人随机接受阿托伐他汀(n=44),瑞舒伐他汀(n=45),和匹伐他汀(n=42),治疗6个月。
结果:分配给阿托伐他汀(-3.5mg/dL,p=0.42)和瑞舒伐他汀(-6.5mg/dL,p=0.17),而在接受匹伐他汀治疗的患者中下降更多(-19.0mg/dL,p<0.001)。在阿托伐他汀治疗期间,平均糖化血红蛋白A1c(HbA1c)值保持不变(-0.10%,p=0.53)和瑞舒伐他汀(0.20%,p=0.40),但用匹伐他汀(-0.75%,p=0.01)。阿托伐他汀,瑞舒伐他汀,和匹伐他汀显著降低(p<0.001)血浆总胆固醇水平,低密度脂蛋白胆固醇,和甘油三酯,而匹伐他汀组高密度脂蛋白胆固醇(HDL-C)水平显着增加(p=0.04)。
结论:本研究结果表明,匹伐他汀对T2DM合并血脂异常患者FPG和HbA1c的影响小于阿托伐他汀和瑞舒伐他汀。三种他汀类药物的降脂疗效无显著差异,除了HDL-C,与匹伐他汀显著增加。虽然匹伐他汀在稳定的抗糖尿病治疗期间对T2DM患者血糖稳态的药理作用机制尚不清楚,可以认为匹伐他汀与降血糖药的药物相互作用较小,或者它增加了血浆脂联素水平。
OBJECTIVE: Diabetes and dyslipidemia are leading causes of mortality and morbidity. According to international guidelines, statins are the cornerstone of treatment in patients with diabetes and/or dyslipidemia. However, statins and antidiabetic agents have opposite pharmacological effects, because statins, particularly atorvastatin and rosuvastatin, impair glucose homeostasis, increasing the risk of new-onset diabetes, whereas antidiabetic drugs improve glycemic homeostasis. The aim of this
study was to investigate the effect of atorvastatin, rosuvastatin, and
pitavastatin on glucose homeostasis in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia during stable treatment with hypoglycemic drugs.
METHODS: The
study was conducted as a pilot, prospective, randomized, open label, parallel group with blinded-endpoints (PROBE)
study. Of 180 recruited patients with T2DM and dyslipidemia, 131 were randomized to atorvastatin (n=44), rosuvastatin (n=45), and pitavastatin (n=42) and treated for 6 months.
RESULTS: Fasting plasma glucose (FPG) marginally decreased in patients assigned to atorvastatin (-3.5 mg/dL, p=0.42) and rosuvastatin (-6.5 mg/dL, p=0.17), while it decreased much more in patients treated with pitavastatin (-19.0 mg/dL, p<0.001). Mean glycated hemoglobin A1c (HbA1c ) values remained unchanged during treatment with atorvastatin (-0.10%, p=0.53) and rosuvastatin (0.20%, p=0.40), but were significantly reduced with pitavastatin (-0.75%, p=0.01). Atorvastatin, rosuvastatin, and pitavastatin significantly lowered (p<0.001) plasma levels of total cholesterol, low-density lipoprotein-cholesterol, and triglycerides, while high-density lipoprotein-cholesterol (HDL-C) levels increased significantly (p=0.04) only in the pitavastatin group.
CONCLUSIONS: The results of the present
study suggest that
pitavastatin affects FPG and HbA1c less than atorvastatin and rosuvastatin in patients with T2DM and concomitant dyslipidemia. Lipid-lowering efficacies were not significantly different among the three statins, with the exception of HDL-C, which increased significantly with pitavastatin. Although the pharmacological mechanism of pitavastatin on glucose homeostasis in patients with T2DM during stable antidiabetic therapy is not known, it can be assumed that
pitavastatin has less drug interaction with hypoglycemic agents or that it increases plasma levels of adiponectin.