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.
Patients and 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 (HbA_1c), 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 HbA_1c (-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 HbA_1c (-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 HbA_1c (-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 HbA_1c 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.
Conclusion Nateglinide appears to improve glycemic control as well as the levels of some prothrombotic parameters compared to glibenclamide when administered in combination with metformin.