Title:A Pilot Study of Exenatide Actions in Alzheimer’s Disease
Volume: 16
Issue: 8
关键词:
GLP-1激动剂，exenatide，记忆，糖尿病，安慰剂，阿尔茨海默病。
摘要:
Background: Strong preclinical evidence suggests that exenatide, a glucagon-like peptide-1 (GLP-
1) receptor agonist used for treating type 2 diabetes, is neuroprotective and disease-modifying in Alzheimer’s
Disease (AD).
Objective: We performed an 18-month double-blind randomized placebo-controlled Phase II clinical trial to
assess the safety and tolerability of exenatide and explore treatment responses for clinical, cognitive, and biomarker
outcomes in early AD.
Method: Eighteen participants with high probability AD based on cerebrospinal fluid (CSF) biomarkers completed
the entire study prior to its early termination by the sponsor; partial outcomes were available for twentyone.
Results: Exenatide was safe and well-tolerated, showing an expectedly higher incidence of nausea and decreased
appetite compared to placebo and decreasing glucose and GLP-1 during Oral Glucose Tolerance Tests.
Exenatide treatment produced no differences or trends compared to placebo for clinical and cognitive measures,
MRI cortical thickness and volume, or biomarkers in CSF, plasma, and plasma neuronal extracellular
vesicles (EV) except for a reduction of Aβ42 in EVs.
Conclusion: The positive finding of lower EV Aβ42 supports emerging evidence that plasma neuronal EVs
provide an effective platform for demonstrating biomarker responses in clinical trials in AD. The study was
underpowered due to early termination and therefore we cannot draw any firm conclusions. However, the
analysis of secondary outcomes shows no trends in support of the hypothesis that exenatide is diseasemodifying
in clinical AD, and lowering EV Aβ42 in and of itself may not improve cognitive outcomes in AD.
