Effect of Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin on Plasminogen Activator Inhibitor-1 in Patients With Diabetes Mellitus

• Published in: The American journal of cardiology Vol. 115; no. 4; pp. 454 - 460
• Main Authors: Tani, Shigemasa, MD, Takahashi, Atsuhiko, MD, Nagao, Ken, MD, Hirayama, Atsushi, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2015; Elsevier Limited
• Subjects: Adamantane - administration & dosage; Adamantane - analogs & derivatives; Adipocytes; Aged; Apolipoproteins; Blood Glucose - metabolism; Cardiovascular; Cardiovascular disease; Cardiovascular Diseases - blood; Cardiovascular Diseases - complications; Cardiovascular Diseases - drug therapy; Cholesterol; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Drug use; Female; Follow-Up Studies; Glycated Hemoglobin A - metabolism; Heart attacks; Homeostasis; Humans; Hypertension; Insulin; Insulin resistance; Lipids; Low density lipoprotein; Male; Metabolism; Middle Aged; Nitriles - administration & dosage; Particle size; Physiology; Plasminogen Activator Inhibitor 1 - blood; Prospective Studies; Pyrrolidines - administration & dosage; Regression analysis; Substance abuse treatment; Time Factors; Treatment Outcome
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/j.amjcard.2014.11.044

Dipeptidyl peptidase-4 (DPP-4) inhibitors may affect the serum levels of plasminogen activator inhibitor-1 (PAI-1) associated with triglyceride (TG) metabolism, which is a prognostic factor for cardiovascular disease, in diabetic patients. We conducted an 8-week, prospective, randomized study in which we assigned type 2 diabetic patients who were inadequately controlled with antidiabetic therapy to the vildagliptin group (50 mg bid, n = 49) or the control group (n = 49). The primary efficacy parameter was the change in the serum level of PAI-1, and the secondary end point was the change in the serum levels of TG-rich lipoproteins. In the vildagliptin group, significant decrease of the serum PAI-1 level by 16.3% (p <0.0001) and significant decreases of the serum TG, remnant-like particle cholesterol, and apolipoprotein B levels by 12.1% (p = 0.002), 13.9% (p = 0.003), and 9.5% (p <0.0001), respectively, were observed. No such changes were observed in the control group. Multivariate regression analyses identified the absolute change from the baseline (Δ) of the PAI-1, but not that of the fasting blood glucose or hemoglobin A1c, as independent predictors of the ΔTG, Δ remnant-like particle cholesterol, and Δ apolipoprotein B. In conclusion, treatment of type 2 diabetes with vildagliptin might prevent the progression of atherosclerotic cardiovascular disease in diabetic patients by decreasing the serum PAI-1 levels and improving TG metabolism.