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The Differential Effects of Metformin on Markers of Endothelial Activation and Inflammation in Subjects with Impaired Glucose Tolerance: A Placebo-Controlled, Randomized Clinical Trial

Clinical Research Center (A.E.C.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; and Departments of Endocrinology and Metabolism (A.D., C.A.A.-S., A.N.H., J.L.C., F.J.G.-P.), Radiology (T.C.), and Medicine (J.A.R.), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan 14000, Mexico City, Mexico

Address all correspondence and requests for reprints to: Carlos A. Aguilar-Salinas, M.D., Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga Number 15, Tlalpan 14000, Mexico City, Mexico. E-mail: caguilarsalinas{at}yahoo.com.

The effect of metformin (1000 mg twice a day) on markers of endothelial activation, inflammation, and coagulation was investigated in subjects with impaired glucose tolerance (IGT) in a 16-wk, randomized, placebo-controlled, double-blind study. Soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, C-reactive protein, TNF, von Willebrand factor, and tissue plasminogen activator were measured at baseline and at the end of the trial. Subjects with IGT (n = 55, 14 males and 41 females), aged 48.4 ± 9.6 yr with a body mass index of 31.4 ± 5.6 kg/m², were studied. All participants followed a 1-month stabilization period in their diet and physical activity. Afterward, 29 subjects were assigned to the treatment group and 26 to the control group. A significant reduction in weight, fasting plasma glucose, soluble intercellular adhesion molecule (306 ± 75 vs. 268 ± 61 ng/ml, P = 0.029), soluble vascular cell adhesion molecule (595 ± 114 vs. 508 ± 126 ng/ml, P = 0.006), and von Willebrand factor (124 ± 34 vs. 94 ± 34%, P = 0.001) was seen in the treatment group, whereas tissue plasminogen activator, TNF, and C-reactive protein levels did not change. No change was seen in the control group. Thus, metformin improves the plasma levels of some markers of endothelial activation and coagulation in subjects with IGT, whereas it has no effect on markers of inflammation.

This work was supported by a grant from Silanes Laboratories through FunSalud, a nonprofit health care organization in Mexico.

Abbreviations: A1c, Hemoglobin A_1C; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CRP, C-reactive protein; FPG, fasting plasma glucose; HDL, high-density lipoprotein; HOMA, homeostasis model of assessment; IGT, impaired glucose tolerance; IR, insulin resistance; LDL, low-density lipoprotein; PAI-1, plasminogen-activator inhibitor 1; sICAM, soluble intercellular adhesion molecule; sVCAM, soluble vascular cell adhesion molecule; tPA, tissue plasminogen activator; vWF, von Willebrand factor.

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