Association between exenatide use and incidence of Alzheimer's disease

Abstract

Introduction Recent developments suggest that insulin‐sensitizing agents used to treat type II diabetes (T2DM) may also prove useful in reducing the risk of Alzheimer's disease (AD). The objective of this study is to analyze the association between exenatide use among Medicare beneficiaries with T2DM and the incidence of AD. Methods We performed a retrospective cohort analysis on claims data from a 20% random sample of Medicare beneficiaries with T2DM from 2007 to 2013 (n = 342,608). We compared rates of incident AD between 2009 and 2013 according to exenatide use in 2007–2008, measured by the number of 30‐day‐equivalent fills. We adjusted for demographics, comorbidities, and use of other drugs. Unmeasured confounding was assessed with an instrumental variables approach. Results The sample was mostly female (65%), White (76%), and 74 years old on average. Exenatide users were more likely to be male (38% vs. 35%), White (87% vs. 76%), and younger (by 4.2 years) than non‐users. Each additional 30‐day‐equivalent claim was associated with a 2.4% relative reduction in incidence (odds ratio 0.976; 95% confidence interval 0.963–0.989; P < .001). There was no evidence of unmeasured confounding. Discussion Exenatide use is associated with a reduced incidence of AD among Medicare beneficiaries aged 65 years or older with T2DM. The association shown in this study warrants consideration by clinicians prescribing insulin sensitizing agents to patients.

Mechanistic Insights for Drug Repurposing and the Design of Hybrid Drugs for Alzheimer’s Disease

“…Recently, a longitudinal cohort analysis was conducted on patients suffering from T2D, and later AD, by comparing the rates of AD incidence in exenatide-treated and untreated patients within the period 2009 to 2013. 91 The AD incidence was found to be lower in exenatide-treated patients, wherein the MOA is attributed to the reduced activation of the PI3K/Akt signaling pathway (Figure 5A). After crossing the BBB, exenatide binds to GLP1R in the CNS and restores the proper functioning of the PI3K/Akt signaling pathway.…”

“…Nevertheless, the inconclusive results, small scale of study, and early termination of the study led to extensive clinical trials to access the therapeutic efficacy of exenatide. Recently, a longitudinal cohort analysis was conducted on patients suffering from T2D, and later AD, by comparing the rates of AD incidence in exenatide-treated and untreated patients within the period 2009 to 2013 . The AD incidence was found to be lower in exenatide-treated patients, wherein the MOA is attributed to the reduced activation of the PI3K/Akt signaling pathway (Figure A).…”

“…The AD incidence was found to be lower in exenatide-treated patients, wherein the MOA is attributed to the reduced activation of the PI3K/Akt signaling pathway (Figure A). After crossing the BBB, exenatide binds to GLP1R in the CNS and restores the proper functioning of the PI3K/Akt signaling pathway. , Additionally, exenatide treatment ameliorates τ-toxicity by reducing phosphorylation at the Ser199, Ser202, and Thr217 residues in the hippocampus of T2D mice . Wang and co-workers treated AD mice (C57BL/6) with exenatide and observed improvement in learning, memory deficits, and circadian rhythm .…”

Dysmetabolism and Neurodegeneration: Trick or Treat?

“…Sitagliptin reversed nigrostriatal degeneration, improved motor performance, and rescued the memory deficits in rotenone-lesioned PD-like rats [ 286 , 292 ]. The use of DPP4 inhibitors and GLP-1 mimetics is associated with a lower risk for PD and AD among patients with T2D, even compared to the use of other oral antidiabetic drugs [ 293 , 294 ]. All together, these clearly state that the decrease in insulin resistance and the regulation of whole-body glucose homeostasis, and therefore a better metabolic control, is associated with better cognitive function and slower deterioration of brain capacities related to the neurodegenerative process.…”

Systematic search for peptide and protein ligands of human serum albumin capable of affecting its interaction with amyloid β peptide

“…Лираглутид, семаглутид и эксенатид снижают риск развития БА у пациентов с диагнозом сахарного диабета 2-го типа (по данным ресурса Alzforum и B. Zhou и соавт. [37]). В то же время эксенатид пока не по казал положительных эффектов в лечении БА [38].…”