Effects of pioglitazone and vildagliptin on coagulation cascade in diabetes mellitus--targeting thrombogenesis.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is intricately allied with an increased risk of atherothrombotic disease. Thrombosis is the cause of mortality in 80% of patients with diabetes mellitus. Endothelial abnormalities lead to elevated inflammatory and coagulation biomarkers as seen in diabetes. Progression of atherothrombotic disease in diabetes has been linked with elevated levels of various coagulation factors including fibrinogen, plasminogen activator inhibitor-1, and von Willebrand factor.


METHODS
We review the existing evidence and most recent data elucidating the various inflammatory and coagulation biomarkers that are elevated in T2DM leading to thrombosis as well as the anti-inflammatory, anticoagulant and antithrombotic mechanisms of pioglitazone and vildagliptin in addition to their effect on glucose metabolism that may halt the progression of atherothrombotic disease.


CONCLUSIONS
The review highlights the pleiotropic effects of pioglitazone and vildagliptin on metabolic, inflammatory and coagulation processes that have the potential to influence cardiovascular disease progression at various points in the disease process, including hemostatic disturbances, inflammation, plaque rupture and atherogenesis in T2DM. Finally, the paper suggests a possible decline in T2DM-associated cardiovascular comorbidities once the antithrombotic potential of pioglitazone and vildagliptin is established through clinical investigation.
Jamia Hamdard (Hamdard University), Faculty of Pharmacy, Research Scholar Department of Pharmacology, New Delhi - 110062, India.
Sana
S
Khan
Saba
S
Khan
Mohammed
M
Imran
Krishna Kolappa
KK
Pillai
Mohd
M
Akhtar
Abul Kalam
AK
Najmi
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D018450:Disease Progression; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D000077205:Pioglitazone; D011759:Pyrrolidines / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D000077597:Vildagliptin
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D001779:Blood Coagulation Factors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005343:Fibrinolytic Agents; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D045162:Thiazolidinediones; D000077597:Vildagliptin; D000218:Adamantane; D000077205:Pioglitazone