Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: A randomized clinical trial

Background & aims: Given the long term benefits observed with metformin use in diabetes patients, a role in modulating oxidative stress is imputable. Effects of metformin on markers of oxidative stress, antioxidant reserve, and HDL-c associated antioxidant enzymes were investigated. Methods: In a clinical trial setting (Registered under Clinical Trials.gov Identifier no. NCT01521624) 99 medication-naive, newly diagnosed type 2 diabetes patients were randomly assigned to either metformin or lifestyle modification. AOPP, AGE, FRAP, activities of LCAT, and PON were measured at baseline and after 12-weeks. Results: Baseline values of the oxidative stress markers did not differ significantly between the two groups. In cases, after three months treatment, there was a significant reduction in AOPP (137.52 +/- 25.59, 118.45 +/- 38.42, p < 0.001), and AGE (69.28 +/- 4.58, 64.31 +/- 8.64, p = 0.002). FRAP and PON increased significantly (1060.67 +/- 226.69, 1347.80 +/- 251.40, p < 0.001 and 29.85 +/- 23.18, 37.86 +/- 27.60, p = 0.012 respectively). LCAT levels remained unchanged (45.23 +/- 4.95, 46.15 +/- 6.28, p = 0.439). Comparing the two groups in a final multivariate model, AOPP, FRAP, and AGE levels changed more significantly in metformin compared with lifestyle modification alone (p = 0.007, p < 0.001 and p < 0.001 respectively). Escalation in LCAT or PON activities did not differ between the two groups (p = 0.199 and 0.843 respectively). Conclusions: Use of metformin is more effective in reducing oxidative stress compared with lifestyle modification alone. (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.