Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
Pharmacol Rep. 2013;65(5):1311-6. doi: 10.1016/s1734-1140(13)71489-0.
Fibrates were found to reduce cytokine release and low-grade inflammation in patients with impaired glucose tolerance. The aim of this study was to investigate whether these effects of fibrates may be potentiated by metformin treatment.
The study included 43 patients with isolated impaired glucose tolerance and normal plasma lipids who had been treated for at least 6 months with micronized fenofibrate (200 mg daily). These subjects were randomly assigned to 12 weeks' treatment with either high dose metformin (3 g daily in three divided doses) or placebo. Plasma lipids, glucose homeostasis markers, monocyte cytokine release and plasma C-reactive protein levels were determined before randomization and at the end of the treatment.
Metformin treatment reduced plasma C-reactive protein levels and monocyte release of tumor necrosis factor-α and interleukin-6, as well as tended to reduce monocyte release of interleukin-1β and monocyte chemoattractant protein-1, which was accompanied by an improvement in insulin sensitivity.
Our results show that high-dose metformin produces monocyte-suppressing and systemic anti-inflammatory effects in fibrate-treated patients with isolated impaired glucose tolerance. This suggests that fibrate-metformin combination therapy may bring clinical benefits to impaired glucose tolerance patients at high cardiovascular risk.
贝特类药物已被发现可减少糖耐量受损患者细胞因子释放和低水平炎症。本研究旨在探讨二甲双胍治疗是否可增强贝特类药物的这些作用。
该研究纳入了 43 例单纯性糖耐量受损且血脂正常的患者，这些患者至少接受了 6 个月的微粒化非诺贝特（每日 200mg）治疗。这些患者被随机分配接受 12 周的高剂量二甲双胍（每日 3g，分 3 次服用）或安慰剂治疗。在随机分组前和治疗结束时测定血脂、糖代谢标志物、单核细胞细胞因子释放和血浆 C 反应蛋白水平。
二甲双胍治疗可降低血浆 C 反应蛋白水平和单核细胞释放的肿瘤坏死因子-α和白细胞介素-6，且有降低单核细胞释放白细胞介素-1β和单核细胞趋化蛋白-1的趋势，同时改善胰岛素敏感性。
我们的结果表明，高剂量二甲双胍可在单独接受贝特类药物治疗的糖耐量受损患者中产生抑制单核细胞和全身抗炎作用。这提示贝特类药物-二甲双胍联合治疗可能会给高心血管风险的糖耐量受损患者带来临床获益。
