Effect of Certain Oral Anti Diabetic Drugs on Coagulation Cascade in Diabetes Mellitus

Patil T. R., Patil S. T., Patil S., Patil A.

Abstract


Thrombotic events in diabetics contribute for almost 65-80% of cardiovascular events. Diabetes affects the platelet, the
coagulation factors and fibrinolytic system leading to a state of hypercoagulation and hypofibrinolysis resulting in to
thrombosis. Oral drugs commonly used in management of type II diabetes mellitus are antidiabetics like metformin, PPAR-
γ agonist and DPP-4 inhibitor. They rarely produce hypoglycemia. Metformin has been proved to prevent release of
mtDNA from arachidonic acid stimulated platelets, reduce membrane damage and mitochondrial ROS production in the
platelets. Similarly processes like platelet adhesion, activation and aggregation on collagen coated surfaces which initiate
thrombosis are prevented by metformin. PPAR- γ agonists like pioglitazone and rosiglitazone have anti atherogenic effect.
They decrease the expression of inflammatory markers and affect the coagulation markers like factor VII: C and inhibit
platelet activation. Pioglitazone also reduces the VLDL, triglycerides and increases HDL which further contributes in
attenuation of atherosclerosis. DPP-4 inhibitors, which are relatively newer class of antidiabetics, having minimum
potential for hypoglycemia induction, due to their novel mechanism of action. Studies have proved that long term use of
DPP-4 inhibitors have reduced cardiac mortality by their lipid lowering action, increased release of NO from endothelium
and inhibition of TNF- α, PAI-1 and VCAM expression. Increased levels of stromal cell derived factor - 1α helps to
maintain endothelial homeostasis and vascular repair. Decreased oxidative stress, inhibition of inflammatory genes like IL-
6, IL-12, TNF- α provide additional benefit. Destabilization of vasculo-atherosclerotic plaque is prevented by DPP-4
inhibitors. Thus these oral antidiabetics drugs offer many benefits beyond blood glucose control which prevent
atherosclerosis, inhibits hypercoagulable state and enhances fibrinolysis which translates into decreased cardiac
complications in diabetes

Keywords


Oral Antidiabetics, Meformin, mtDNA.

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DOI: https://doi.org/10.25258/ijtpr.v9i03.9078

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