Effects of a vildagliptin/metformin combination on markers of atherosclerosis, thrombosis, and inflammation in diabetic patients with coronary artery disease.
BACKGROUND
Diabetic patients present with an accelerated atherosclerotic process and an increased risk for future cardiovascular events. In addition to the risk imposed by the disease itself, pharmacological treatment adds also a sizable risk, especially if certain classes of antidiabetic drugs are employed. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors have anti-atherosclerotic effects, yet clinical data are scarcely available.


METHODS
We plan to prospectively investigate the effects of dipeptidyl peptidase-4 inhibition with vildagliptin on a number of atherothrombotic markers and adipokines in patients with proven atherosclerosis and type 2 diabetes. The selected markers are: interleukin-6, high sensitivity C reactive protein, interleukin 1-beta, total adiponectin levels, matrix metallo-proteinase 9 and platelet reactivity testing. Sixty eligible patients will be randomized in a 2:1 ratio to vildagliptin/metformin or metformin only treatment, for a 3-month duration treatment. Blood sampling for the proposed investigations will be taken at enrollment and immediately after completion of the study period.


CONCLUSIONS
Demonstrating antiatherothrombotic properties of dipeptidyl peptidase-4 inhibitors on proven markers is of substantial clinical significance. Coupled with their proven good safety profile these findings could translate into a significant clinical benefit.
Cardiac Rehabilitation Institute, Leviev Heart Center, Sheba Medical Center, 52621, Tel Hashomer, Israel. Robert.Klemper@sheba.health.gov.il
Robert
R
Klempfner
Jonathan
J
Leor
Alexander
A
Tenenbaum
Enrique Z
EZ
Fisman
Ilan
I
Goldenberg
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D052242:Adiponectin / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007557:Israel; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D000077597:Vildagliptin
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D007004:Hypoglycemic Agents; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D009570:Nitriles; D011759:Pyrrolidines; D002097:C-Reactive Protein; D008687:Metformin; D020780:Matrix Metalloproteinase 9; D000077597:Vildagliptin; D000218:Adamantane