Antioxidant effects of gliclazide, glibenclamide, and metformin in patients with type 2 diabetes mellitus

Abstract Background: Hyperglycemia increases oxygen-reactive species generation and reduces the protective capabilities of antioxidant defense systems. In patients with type 1 or 2 diabetes mellitus (DM), the increased production of oxygen free radicals may be linked to the development of chronic complications of diabetes. In vitro studies have demonstrated that oral antidiabetic drugs have antioxidant effects that might be secondary to an inhibiting role in lipid peroxidation. Objective: The purpose of this study was to determine the effects of 3 common oral antidiabetic agents on oxidized anti-low-density lipoprotein antibody (o-LAb) plasma levels and on total antioxidant status (TAS). Methods: We studied in vivo patients with type 2 DM treated with long-term gliclazide, glibenclamide, or metformin therapy along with healthy control subjects. The diabetic patients were randomized to the following treatment groups: group 1, gliclazide 80 to 240 mg/d; group 2, glibenclamide 10 to 15 mg/d; and group 3, metformin 1500 mg/d. Results: Ninety-two patients with type 2 DM (group 1, 18 females, 15 males [mean age, 62.8 ± 9.5 years]; group 2, 19 females, 11 males [mean age, 63.2 ± 8.8 years]; group 3, 16 females, 13 males [mean age, 62.0 ± 5.3 years]) and 28 age- and sex-matched healthy control subjects (18 females, 10 males; mean age, 59.1 ± 5.3 years) were enrolled. In group 1, both the o-LAb level and TAS were similar to those of the control group. The o-LAb level was highest and the total antioxidant plasma level was lowest in group 3, whereas intermediate levels were found in group 2. Multivariate analysis using stepwise regression showed that the type of oral antidiabetic agent was independently associated with o-LAb and total antioxidant levels, as well as with sex, age, and type of antidiabetic agent. Conclusion: In the patients with type 2 DM in this study, gliclazide had a positive effect on the oxidation-reduction system.