Dapagliflozin Modulates MicroRNA Expression in Type 2 Diabetes Patients with Diabetic Nephropathy: A Retrospective Study

Objective: Diabetic nephropathy (DN) is one of the most serious microvascular complications of Diabetes Mellitus, the prevalence and mortality of which are increasing. Recently, microRNAs (miRNAs) used in the pathogenesis and diagnosis of many diseases have been identified. In this study investigate the relationship between albuminuria and miRNA levels in patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, and to elucidate the potential nephroprotective effects of dapagliflozin through miRNA modulation. Methods: This retrospective study included 47 T2DM patients (25 male, 22 female) with diabetic nephropathy (DN) treated with dapagliflozin. Blood samples were collected at baseline (day 0) and after approximately 60 days of treatment. Levels of miRNA-21, miRNA-141, and miRNA-377 were analyzed using real-time PCR. Clinical and laboratory parameters, including glucose, HbA1c, urine albumin and protein levels, were also assessed. Statistical analysis included the Wilcoxon signed-rank test and Spearman's rank correlation test. Results: Significant decreases were observed in glucose, HbA1c, urinary protein, and albumin levels after dapagliflozin treatment (p<0.01). miRNA-21, miRNA-141, and miRNA-377 levels also decreased significantly following treatment (p<0.01). A positive correlation was found between day 0 miRNA-377 levels and day 0 serum glucose levels. A negative correlation was observed between day 0 miRNA-21 levels and day 60 HbA1c levels. No significant correlations were found between miRNA levels and urine albumin or protein levels. Conclusion: Dapagliflozin treatment in T2DM patients with DN was associated with significant reductions in miRNA-21, miRNA-141, and miRNA-377 levels, alongside improvements in glycemic control and renal function markers. These findings suggest that dapagliflozin may exert its nephroprotective effects partly through modulation of DN-associated miRNAs. Dapagliflozin may be a therapeutic option to treat DN and may be an effective strategy to prevent kidney damage. Further research is warranted to elucidate the mechanisms underlying these effects and to explore the potential of miRNAs as biomarkers or therapeutic targets in DN management.