Effect of metformin combined with lifestyle modification versus lifestyle modification alone on proinflammatory-oxidative status in drug-naïve pre-diabetic and diabetic patients: A randomized controlled study

Background: Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction. Methods: 64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline. Results: Except for HbA1c, baseline values did not differ significantly between the two groups. The post 3-months relative reductions in BMI (P = 0.014) and HbA1c (P = 0.037) in metformin combined with TLC intervention were significantly greater than those in TLC alone group. TNFα plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (−22.90 ± 46.76%, P = 0.01). Conversely, TLC alone basically worsened proinflammatory status (42.40 ± 40.82 %), P < 0.001. Metformin with TLC treatment effected a therapeutic decrement of the oxidative stress (−15.44 ± 35.32%, P = 0.029 vs. baseline) unlike TLC alone (61.49 ± 122.66%, P = 0.01 vs. baseline). Both interventions’ effects were sustained in the 6-month follow up periods. Conclusion: In both intervention groups, the relative changes in plasma TNFα were significantly correlated (P < 0.01) with systolic blood pressure and the relative changes in oxidative stress were markedly correlated (P < 0.05) with total cholesterol.