Investigating changes in fluid biomarkers in early Alzheimer’s disease: design of plasma biomarker analyses and a cerebrospinal fluid sub‐study in the evoke and evoke+ trials of semaglutide versus placebo

Several studies have generated data supporting a role for glucagon‐like peptide 1 receptor agonists (GLP‐1RA) in the treatment of Alzheimer’s disease (AD). For example, GLP‐1RAs reduced neuroinflammation and phospho‐tau accumulation, provided neuroprotective effects, and improved cognitive function in animal model studies. In patients with AD, GLP‐1RAs preserved cerebral glucose metabolism, favorably affected cognition and cortical volume, and in post‐hoc analyses of randomized clinical trials in type 2 diabetes, reduced cognitive impairment and dementia risk. The phase 3 evoke and evoke+ trials (NCT04777396 and NCT04777409, respectively) will assess the efficacy and safety of oral semaglutide (a GLP‐1RA) versus placebo in early AD. Here, we describe how fluid biomarkers will be investigated.