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Article Abstract

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors have potential beneficial effects in Alzheimer's disease (AD).

Methods: We conducted pharmacoepidemiologic studies using two large-scale real-world databases. We fitted covariate-adjusted Cox models to compare the risks of AD among initiators of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors.

Results: We identified GLP-1 receptor agonist initiation compared to DPP-4 inhibitors initiation was associated with a reduced risk of AD (hazard ratio [HR] ≤ 0.69 and P value < 0.001) and SGLT-2 inhibitor initiation compared to DPP-4 inhibitor initiation was associated with a reduced risk of AD (HR ≤ 0.67 and P value < 0.001).

Discussion: GLP-1 receptor agonist initiation and SGLT-2 inhibitor initiation are associated with a reduced risk of AD. Randomized clinical trials are warranted to validate the causal beneficial effects of GLP-1 receptor agonists and SGLT-2 inhibitors in AD.

Highlights: Glucagon-like peptide-1 (GLP-1) receptor agonists are significantly associated with a reduced risk of Alzheimer's disease (AD) compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are significantly associated with a reduced risk of AD compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Two GLP-1 receptor agonists (liraglutide and semaglutide) and three SGLT-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) are associated with a reduced risk of AD in drug-specific sensitivity analyses.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404899PMC
http://dx.doi.org/10.1002/alz.70639DOI Listing

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