Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Glycated hemoglobin and body mass index as mediators of GLP-1RAs and Alzheimer's disease and related dementias in patients with type 2 diabetes.
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Tang Huilin, Donahoo William T, DeKosky Steven T, Lee Yao An, Svensson Mikael, Bian Jiang, Guo Jingchuan
Аннотация
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/m2, 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.
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/m2, 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.