Metformin Improves Both Endothelial Function and Insulin Resistance

The findings support the central role of insulin resistance in the development of endothelial dysfunction and the role of metformin for the treatment of patients with metabolic syndrome.

Metabolic syndrome is associated with impaired endothelial function and increased cardiovascular risk. Insulin resistance is a key feature of metabolic syndrome and plays an important role in the pathogenesis of endothelial dysfunction. The aim of the present study from Italy was to evaluate the effect of metformin on endothelial function and insulin resistance, assessed by the homeostasis model (HOMA-IR, homeostasis model assessment-insulin resistance), in patients with metabolic syndrome. 65 subjects (37 men and 28 women, mean age 54 years) with metabolic syndrome were allocated to receive metformin 500 mg twice daily (n = 32) or placebo (n = 33) for 3 months. Before and after treatment we assessed endothelial function, using flow-mediated dilatation of the brachial artery, and HOMA-IR.

They found: “Patients who received metformin demonstrated statistically significant improvement in endothelium-dependent vasodilation compared with those treated with placebo (from 7.4 to 12.4 vs. 7.3 to 6.9, P = 0.0016, metformin vs. placebo respectively), without significant effect on endothelium-independent response to sublingual glyceryl trinitrate (P =0.32). Metformin improved insulin resistance compared with placebo group (HOMA-IR from 3.39 to 2.5 vs. 3.42 to 3.37; 26% reduction in HOMA-IR, P = 0.01). An association between the improvement in insulin resistance and the improvement in endothelial function (r = 0.58, P = 0.0016) was found.”

The researchers concluded: “Metformin improves both endothelial function and insulin resistance in patients with metabolic syndrome. These findings support the central role of insulin resistance in the development of endothelial dysfunction and the role of metformin for the treatment of patients with metabolic syndrome.”

Journal of Internal Medicine Volume 258 Issue 3 Page 250 September 2005.
appears online Proceedings of the National Academy of Sciences.