Treating cognitive impairment in schizophrenia with GLP-1RAs: an overview of their therapeutic potential

Expert Opin Investig Drugs. 2021 Aug;30(8):877-891. doi: 10.1080/13543784.2021.1951702. Epub 2021 Jul 9.

Abstract

Introduction: Schizophrenia is a neuropsychiatric disorder that affects approximately 1% of individuals worldwide. There are no available medications to treat cognitive impairment in this patient population currently. Preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cognitive function. There is a need to evaluate how GLP-1 RAs alter specific domains of cognition and whether they will be of therapeutic benefit in individuals with schizophrenia.

Areas covered: This paper summarizes the effects of GLP-1 RAs on metabolic processes in the brain and how these mechanisms relate to improved cognitive function. We provide an overview of preclinical studies that demonstrate GLP-1 RAs improve cognition and comment on their potential therapeutic benefit in individuals with schizophrenia.

Expert opinion: To understand the benefits of GLP-1 RAs in individuals with schizophrenia, further preclinical research with rodent models relevant to schizophrenia symptomology are needed. Moreover, preclinical studies must focus on using a wider range of behavioral assays to understand whether important aspects of cognition such as executive function, attention, and goal-directed behavior are improved using GLP-1 RAs. Further research into the specific mechanisms of how GLP-1 RAs affect cognitive function and their interactions with antipsychotic medication commonly prescribed is necessary.

Keywords: Glucagon-like peptide-1 receptor agonists; cognition; executive function; exenatide; liraglutide; memory; metabolic dysregulation; metabolism; schizophrenia; translational assays.

Publication types

  • Review

MeSH terms

  • Animals
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Disease Models, Animal
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Rodentia
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology

Substances

  • Glucagon-Like Peptide-1 Receptor