Inpharma 1460 - 23 Oct 2004

Metformin may directly affectvascular cells

Metformin has beneficial effects on markers ofendothelial activation, but not those of inflammation, inpatients with impaired glucose tolerance, reportresearchers from the US and Mexico.

A total of 55 such patients were randomised to receivemetformin 2 g/day (1 g/day for the first month; n = 29)or placebo, for 16 weeks.*

The metformin group had significant reductionsfrom baseline in plasma levels of soluble intercellularadhesion molecule (sICAM), soluble vascular celladhesion molecule (sVCAM) and von Willebrandfactor (vWF), but not tissue plasminogen activator(tPA), C-reactive protein (CRP) or tumour necrosisfactor-α (TNFα) [see table]. None of these markerssignificantly changed from baseline in the placebogroup.

Markers of endothelial activation, coagulation andinflammation, according to treatment

Metformin group Placebo group

Baseline 16 weeks Baseline 16 weeks

Mean plasma levelssICAM (ng/mL) 306 268*† 296 285sVCAM 595 508*† 580 559(ng/mL)

vWF (%) 124 94*† 113 112tPA (ng/mL) 9.1 9.1 9.1 9.8CRP (mg/L) 5.5 5.4 5.3 5.2TNFα (pg/mL) 5.6 5.4 5.8 5.8

* significantly lower than baseline† significantly greater reduction from baseline than placebo

In addition, the change in vWF levels was significantlycorrelated with the change in sVCAM levels (r = 0.29).After controlling for possible confounding variables in amultiple regression model, the effects of metformin onvWF, sICAM and sVCAM levels remained statisticallysignificant; this suggests that the effects areindependent of the effects of metformin on weight andinsulin sensitivity.* This study received financial support from Silanes Laboratories.

Caballero AE, et al. The differential effects of metformin on markers of endothelialactivation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial. Journal of Clinical Endocrinology andMetabolism 89: 3943-3948, No. 8, Aug 2004 800993010

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Inpharma 23 Oct 2004 No. 14601173-8324/10/1460-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved