This study is a prospective, randomized, open-label trial with blinded outcome assessment (PROBE design) designed to evaluate the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy on cognitive function in adults with type 2 diabetes mellitus (T2D). A total of 200 participants aged 50 years or older with T2D of at least five years' duration and HbA1c ≤8.5% will be randomized in a 1:1 ratio to receive either standard diabetes care plus an SGLT2 inhibitor or standard diabetes care without an SGLT2 inhibitor. Participants will be followed for 12 months.
The primary objective is to compare changes in executive cognitive function between the two treatment groups using a composite cognitive outcome derived from standardized neuropsychological tests. Secondary objectives include assessment of global cognitive function, glycaemic variability measured by continuous glucose monitoring, metabolic control, circulating biomarkers of neurodegeneration and inflammation, functional status, and treatment safety. Baseline brain magnetic resonance imaging (MRI), APOE genotyping, frailty status, sleep quality, psychological well-being, and physical activity will be evaluated as potential modifiers of cognitive outcomes and treatment response.
The study is intended to provide prospective evidence regarding the association between SGLT2 inhibitor therapy and cognitive outcomes in adults with T2D while exploring the metabolic, neurodegenerative, and behavioural factors that may contribute to cognitive changes over time.