Abstract
INTRODUCTION: Due to its metabolic effects, dapagliflozin, a sodium-glucose transporter 2 (SGLT2) inhibitor, holds potential as an Alzheimer's disease (AD) therapeutic. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group, 12-week single-site study to investigate the effect of dapagliflozin in participants with probable AD (Mini-Mental State Examination [MMSE] score 15-26). We planned to enroll 48 participants with 2:1 randomization to 10 mg dapagliflozin once daily (n = 32) versus matching placebo (n = 16). The primary objective was the effect of dapagliflozin on cerebral N-acetylaspartate (NAA). We also assessed safety, glycemic control, body composition, brain metabolism, and cognition. RESULTS: There was no change in the primary outcome. There were no significant adverse event differences. Hemoglobin A1c, fat mass, and fat-free lean mass decreased; brain glutathione increased; and Stroop Interference test (but not other cognitive test) performance improved. DISCUSSION: Treated participants manifested metabolic effects observed in clinical studies of other cohorts. In AD, dapagliflozin use may affect the brain. HIGHLIGHTS: Dapagliflozin did not alter magnetic resonance spectroscopy N-acetylaspartate (primary outcome) in this exploratory Alzheimer's disease (AD) trial. Dapagliflozin-induced glucose disposal is sufficient to alter systemic metabolism. AD patients taking dapagliflozin exhibited metabolic effects seen in diabetics.