Journal Article Randomized Controlled Trial Ppublish
PubMed: 40566796 DOI: 10.1002/alz.70416
Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial.
Alzheimers Dement 21(6):e70416
Authors: Jeffrey M Burns, Jill K Morris, Eric D Vidoni, Heather M Wilkins, In-Young Choi, Phil Lee, Suzanne L Hunt, Jonathan D Mahnken, William M Brooks, Rebecca J Lepping, Aditi Gupta, Russell Esterline, Jan Oscarsson, Russell H Swerdlow
Affiliations
- University of Kansas Medical Center, Kansas City, Kansas, USA.
- Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca Pharmaceuticals, Gaithersburg, Maryland, USA.
- Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden.
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.
MeSH
Sodium-Glucose Transporter 2 Inhibitors, Dementia, Alzheimer Disease, Brain