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We planned to enroll 48 participants with 2:1 randomization to 10\u00a0mg dapagliflozin once daily (<jats:italic>n<\/jats:italic>\u00a0=\u00a032) versus matching placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a016). The primary objective was the effect of dapagliflozin on cerebral <jats:italic>N<\/jats:italic>\u2010acetylaspartate (NAA). We also assessed safety, glycemic control, body composition, brain metabolism, and cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>There was no change in the primary outcome. There were no significant adverse event differences. Hemoglobin A1c, fat mass, and fat\u2010free lean mass decreased; brain glutathione increased; and Stroop Interference test (but not other cognitive test) performance improved.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Treated participants manifested metabolic effects observed in clinical studies of other cohorts. In AD, dapagliflozin use may affect the brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Dapagliflozin did not alter magnetic resonance spectroscopy <jats:italic>N<\/jats:italic>\u2010acetylaspartate (primary outcome) in this exploratory Alzheimer's disease (AD) trial.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Dapagliflozin\u2010induced glucose disposal is sufficient to alter systemic metabolism.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>AD patients taking dapagliflozin exhibited metabolic effects seen in diabetics.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70416","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T02:20:38Z","timestamp":1750904438000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effects of the SGLT2 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