Inflammatory and Metabolic Biomarker Alterations Associated with Long-Term Metformin and Glibenclamide Therapy in Type 2 Diabetes

Abstract

Objective: To evaluate inflammatory cytokine profiles and key metabolic enzyme activities in T2DM patients receiving long-term metformin or glibenclamide therapy, with a view to identifying biochemical signatures associated with altered metabolic responsiveness.

Methods: This comparative cross-sectional study evaluated inflammatory cytokines and metabolic enzyme activities in adults with T2DM receiving long-term metformin or glibenclamide therapy. A total of 125 participants aged ≥30 years were recruited from the Endocrinology Clinic of the University of Benin Teaching Hospital, Nigeria. Subjects had received either metformin or glibenclamide for a minimum of three months. Age and sex matched non-diabetic individuals served as controls. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). Erythrocyte glucose-6-phosphate dehydrogenase (G6PDH) and serum lactate dehydrogenase (LDH) activities were determined using standardized enzymatic assays. Statistical analyses were performed using appropriate parametric tests, with significance set at p < 0.05.

Results: Male patients receiving metformin or glibenclamide exhibited significantly higher IL-1β concentrations compared with non-diabetic controls (p < 0.05), while IL-6 levels showed no consistent significant differences across treatment groups. G6PDH activity was significantly reduced in male patients on both therapies, whereas LDH activity was significantly elevated in both male and female patients, indicating altered redox balance and increased metabolic stress during long-term oral antidiabetic therapy.

Conclusion: Long-term metformin or glibenclamide therapy in individuals with T2DM is associated with measurable alterations in inflammatory and metabolic biomarkers. Elevated IL-1β levels, reduced G6PDH activity and increased LDH activity particularly among male patients, suggest the presence of chronic metabolic stress and inflammatory activation during prolonged oral antidiabetic therapy.