Can dipeptidyl peptidase-4 inhibitors treat cognitive disorders?

Pharmacol Ther. 2020 Aug:212:107559. doi: 10.1016/j.pharmthera.2020.107559. Epub 2020 May 5.

Abstract

The linkage of neurodegenerative diseases with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), including oxidative stress, mitochondrial dysfunction, excessive inflammatory responses and abnormal protein processing, and the correlation between cerebrovascular diseases and hyperglycemia has opened a new window for novel therapeutics for these cognitive disorders. Various antidiabetic agents have been studied for their potential treatment of cognitive disorders, among which the dipeptidyl peptidase-4 (DPP-4) inhibitors have been investigated more recently. So far, DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models, and cognitive benefits in diabetic patients with or without cognitive impairments. This review aims to summarize the potential mechanisms, advantages and limitations, and currently available evidence for developing DPP-4 inhibitors as a treatment of cognitive disorders.

Keywords: Alzheimer's disease; Cerebrovascular disease; Cognitive disorder; Dementia; Dipeptidyl peptidase-4; Inhibitor; Neurodegenerative disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cognitive Dysfunction / drug therapy*
  • Diabetes Mellitus, Type 2 / complications
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Gastric Inhibitory Polypeptide / physiology
  • Gastrointestinal Microbiome / drug effects
  • Glucagon-Like Peptide 1 / physiology
  • Glucagon-Like Peptide-1 Receptor / physiology
  • Humans
  • Insulin Resistance

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1