Effects of nateglinide and glibenclamide on prothrombotic factors in naïve type 2 diabetic patients treated with metformin: a 1-year, double-blind, randomized clinical trial.
OBJECTIVE
To evaluate the effect on coagulation and fibrinolysis parameters and on non-conventional cardiovascular risk factors of metformin plus nateglinide or glibenclamide in naïve type 2 diabetes patients.


METHODS
A total of 248 type 2 diabetic patients were enrolled and randomly assigned to receive nateglinide or glibenclamide, and metformin for 12 months. We assessed body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostasis model assessment index (HOMA index), lipid profile with lipoprotein (a) [Lp(a)], fibrinogen (Fg), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), homocysteine (Hcy), systolic blood pressure (SBP), diastolic blood pressure (DBP).


RESULTS
After 9 months of treatment, both tested drug combinations were similarly associated with a significant reduction in FPG (nateglinide, -17.2%; glibenclamide, -16.9%, both p<0.05) compared to the baseline, while HbA1c (-17.3%, p<0.05) and PPG (-15.2%, p<0.05) significantly decreased only in the nateglinide group. After one year of treatment, compared to the baseline the nateglinide group showed a significant reduction in HbA1c (-21%, p<0.01), FPG (-20.7%), p<0.01, PPG (-21.5%, p<0.05), HOMA index (-25.4%, p<0.05); the glibenclamide group, showed a significant reduction in HbA1c (-11%, p<0.05), FPG (-23.2%, p<0.05), PPG (-11.2%, p<0.05), and HOMA index (-23.9%, p<0.05) but to a minor extent. Moreover, the HbA1c difference value from baseline observed in the nateglinide-treated group was significantly higher than that observed in the glibenclamide group. Therefore the nateglinide-treated patients showed a significant reduction in some prothrombotic parameters (PAI-1=-19%, Lp(a)=-31%, and Hcy=-32.3%, all p<0.05), whereas the glibenclamide-treated patients did not.


CONCLUSIONS
Nateglinide appears to improve glycemic control as well as the levels of some prothrombotic parameters compared to glibenclamide when administered in combination with metformin.
Derosa
Giuseppe
G
Department of Internal Medicine and Therapeutics, University of Pavia, Italy. giuseppe.derosa@unipv.it
D'Angelo
Angela
A
Fogari
Elena
E
Salvadeo
Sibilla
S
Gravina
Alessia
A
Ferrari
Ilaria
I
Cicero
Arrigo F G
AF
D000328:Adult; D003510:Cyclohexanes / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000187:drug effects*
D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D017395:Plasminogen Activator Inhibitor 1; D000077715:Nateglinide; D010649:Phenylalanine; D008687:Metformin; D010959:Tissue Plasminogen Activator; D005905:Glyburide