Oxidative stress injury and glucolipotoxicity in type 2 diabetes mellitus: The potential role of metformin and sitagliptin

Objective: The objective of this study was to explore the potential effects of metformin and/or sitagliptin on the oxidative stress (OS) and antioxidant capacity in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: In this cross-sectional study, 64 patients with T2DM compared with 32 healthy controls, they divided into three groups: Group A: 32 healthy controls, Group B: 33 patients with T2DM on metformin therapy, and Group C: 31 patients with T2DM on metformin plus sitagliptin therapy. Fasting blood glucose, glycated hemoglobin, fasting serum insulin, insulin resistance, lipid profile, cardiac indices, and anthropometric measurements were determined. As well, OS parameters which include total oxidant status (TOS), total antioxidant status (TAS), and OS index (OSI) were measured in patients with T2DM and healthy controls. Data analysis was done using SPSS; for significance testing, unpaired Student's t-test and analysis of variance were used. Pearson correlation was also used to detect the level of correlations. Results: Patients with T2DM have a high risk of diverse cardiometabolic changes compared with the controls (P = 0.0001). TOS was high in diabetic patients (36.89 ± 4.71 μmole/L) compared with the controls (12.74 ± 3.81 μmole/L) (P = 0.0001), TAS was low in diabetic patients (1145.89 ± 293.51 μmole/L) compared with the controls (1237.61 ± 383.74 μmole/L) (P = 0.0001), and OSI was high in diabetic patients (3.21 ± 1.99) compared with the controls (1.02 ± 0.92) (P = 0.0001). Patients with T2DM on metformin plus sitagliptin illustrated low OSI compared with T2DM on metformin monotherapy (P = 0.04). Conclusion: Metformin and/or sitagliptin attenuate T2DM-induced OS through potentiation of TAC and reduction of TOC and OSI. Therefore, a combination of metformin and sitagliptin is recommended to reduce glucolipotoxicity and related OS injury.