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Article Abstract
Introduction: Whether reductions in glycated hemoglobin (HbA1c) levels and body mass index (BMI) mediate the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and Alzheimer's disease and related dementias (ADRD) risk is unknown.
Methods: This cohort study included 22,908 patients aged ≥ 50 years with type 2 diabetes (T2D) newly prescribed GLP-1RA or other second-line glucose-lowering drugs (GLDs). Causal mediation analysis was used to estimate to what extent the effect of GLP-1RAs on ADRD risk was attributable to lowering HbA1c or BMI.
Results: Compared to other GLD users, GLP-1RA users had significant reductions in HbA1c levels by 0.16% and BMI by 0.23 kg/m, along with a 26% lower ADRD risk. The direct protective effect of GLP-1RAs on ADRD risk persisted even after accounting for HbA1c and BMI reductions, with minimal mediation effects observed through these factors.
Discussion: GLP-1RAs reduce ADRD risk, largely independent of their effects on HbA1c and BMI.
Highlights: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were associated with reductions in glycated hemoglobin (HbA1c) and body mass index (BMI) compared to other second-line glucose-lowering drugs(GLDs). GLP-1RA users were associated with a 26% lower risk of Alzheimer's disease and related dementias (ADRD) than other GLD users. The protective effect of GLP-1RAs against ADRD in adults with type 2 diabetes (T2D) is largely independent of their effects on HbA1c and BMI.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982930 | PMC |
| http://dx.doi.org/10.1002/alz.70161 | DOI Listing |
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