Study of the Potential Neuroprotective Effects of Dapagliflozin (SGLT-2 Inhibitor) in Diabetic Rats

Background: Type 2 diabetes mellitus (T2DM) is increasingly associated with cognitive impairment due to insulin resistance, oxidative stress, and neuroinflammation. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) may provide neuroprotective effects beyond glycemic control. This study aimed to evaluate the potential neuroprotective effects of Dapagliflozin against cognitive impairment in a type 2 diabetic rat model. Methods: Thirty-two adult male albino rats were randomly assigned into four groups (n = 8 each): normal control (NC), normal + dapagliflozin (ND), diabetic control (DC), and diabetic + dapagliflozin (DD). Diabetes was induced by a high-fat diet and low-dose streptozotocin (35 mg/kg). Dapagliflozin (1 mg/kg/day, orally) was given for eight weeks. Results: Blood glucose levels significantly differed among groups (F = 29.11, p < 0.001), with DC showing the highest value (190.13 ± 18.67 mg/dL), and DD demonstrating a marked reduction versus DC (164.75 ± 14.42 mg/dL, p = 0.008). T-maze alternation percentage improved in DD compared to DC (73.31 ± 2.33 vs. 66.78 ± 5.23, p = 0.046). In the open-field test, locomotor activity (squares crossed) was higher in DD than DC (101.75 ± 2.60 vs. 89.13 ± 6.38, p = 0.004), and rearing frequency increased (14.38 ± 1.19 vs. 11.38 ± 2.50, p = 0.015). Fecal pellet count, an anxiety indicator, was significantly lower in DD than DC (1.63 ± 0.52 vs. 3.25 ± 0.46, p < 0.001). Conclusion: Dapagliflozin improved glycemic control, enhanced neuronal activation, and mitigated behavioral and cognitive deficits in diabetic rats, indicating a potential neuroprotective effect against diabetes-induced neurodegeneration.