The research of dapagliflozin on cognitive function in middle-aged and older patients with type 2 diabetes mellitus and mild cognitive impairment: a 36-week prospective parallel control study.

Sodium-glucose co-transporter 2 inhibitors have demonstrated potential for improving cognitive function in preclinical studies; however, robust clinical evidence supporting this effect in humans remains limited. We conducted a prospective trial to assess the effect of dapagliflozin on cognitive function in middle-aged and older patients with type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI). Ninety participants were randomly assigned to either the dapagliflozin or control group for 36 weeks. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Eight participants from each group underwent resting-state functional magnetic resonance imaging to assess region homogeneity (ReHo). After 36 weeks, the dapagliflozin group demonstrated significant improvements in MoCA and MMSE scores compared to the control group. Additionally, the dapagliflozin group exhibited reductions in diastolic blood pressure, glycated haemoglobin, fasting plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and ReHo values in the left superior temporal gyrus were significantly reduced (p < 0.05). Spearman's correlation analysis revealed that improvements in MOCA scores before and after treatment were negatively correlated with HOMA-IR (r = -0.653, p = 0.006), TC (r = -0.619, p = 0.011), and ReHo values in the left superior temporal gyrus (r = -0.710, p = 0.002) in both groups. These findings suggest that dapagliflozin may improve cognitive function and modulate ReHo values in the left superior temporal gyrus in middle-aged and older adults with T2DM. These effects may be linked to improvements in insulin sensitivity and reductions in TC.