Sirtori C R, Franceschini G, Gianfranceschi G, Sirtori M, Montanari G, Bosisio E, Mantero E, Bondioli A
J Cardiovasc Pharmacol. 1984 Sep-Oct;6(5):914-23. doi: 10.1097/00005344-198409000-00027.
The clinical activity of metformin (N,N-dimethyl biguanide), a widely used antidiabetic agent, on arterial blood flow was evaluated in 15 patients with peripheral atherosclerosis. Flow was determined by quantitative strain-gauge plethysmography; plasma lipid, lipoprotein, and apoprotein levels were repeatedly tested during the cross-over trial, comparing 6 months of drug and placebo administration. Metformin (850 mg tid) significantly increased arterial flow after a standardized ischemia (+17.3% after 3 months and +40.0% after 6 months). The increase in arterial flow was reversible after the switch to placebo was made. The drug was similarly effective, although to a lesser extent (+18.6% after 6 months), when given after the placebo. A highly significant effect of drug treatment, as well as of the sequence of administration, could be established by analysis of variance. In spite of the minimal changes of plasma lipid levels during metformin, a highly significant increase of high density lipoprotein cholesterol (+ 8.3% during the whole treatment) was demonstrated; plasma levels of isoprotein AI-1 were also raised during the metformin period. This controlled experiment confirms data from previous open studies, as well as from a longstanding clinical experience. Although the mechanism of the metformin effect cannot, at present, be defined, the reported results indicate that treatments not markedly affecting plasma lipid-lipoprotein levels may improve vascular function in selected arterial districts.
二甲双胍（N，N-二甲基双胍）是一种广泛使用的抗糖尿病药物，我们评估了其对15例外周动脉粥样硬化患者动脉血流的临床活性。血流通过定量应变计体积描记法测定；在交叉试验期间反复检测血浆脂质、脂蛋白和载脂蛋白水平，比较药物和安慰剂给药6个月的情况。二甲双胍（850毫克，每日三次）在标准化缺血后显著增加动脉血流（3个月后增加17.3%，6个月后增加40.0%）。切换到安慰剂后，动脉血流的增加是可逆的。在服用安慰剂后给药时，该药物同样有效，尽管程度较小（6个月后增加18.6%）。通过方差分析可以确定药物治疗以及给药顺序的高度显著效果。尽管在服用二甲双胍期间血浆脂质水平变化极小，但高密度脂蛋白胆固醇显著增加（整个治疗期间增加8.3%）；在服用二甲双胍期间，血浆异蛋白AI-1水平也升高。这个对照实验证实了先前开放研究以及长期临床经验的数据。尽管目前尚无法确定二甲双胍作用的机制，但报告的结果表明，对血浆脂质-脂蛋白水平影响不明显的治疗可能会改善特定动脉区域的血管功能。
