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Drug Development.

Apostolos Manolopoulos1, Konstantinos Malandris2, Josephine M Egan1

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show modest benefits for Parkinson's disease motor function and hypothalamic obesity BMI reduction. However, they do not improve cognition in Alzheimer's disease or outcomes in stroke and IIH.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Clinical Trials

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for diabetes, obesity, and sleep apnea.
  • GLP-1 receptors in the brain suggest potential therapeutic applications for neurological disorders.

Purpose of the Study:

  • To systematically review and meta-analyze the efficacy of GLP-1RAs in neurological conditions.
  • Evaluate GLP-1RA effectiveness in Alzheimer's disease, Parkinson's disease, stroke, IIH, and hypothalamic obesity.

Main Methods:

  • Systematic review and meta-analysis of randomized controlled trials (RCTs).
  • Searched MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov.
  • Assessed risk of bias and certainty of evidence using GRADE approach.

Main Results:

  • GLP-1RAs did not improve memory/cognition in Alzheimer's disease (low-certainty evidence).
  • GLP-1RAs improved motor function (ON state) in Parkinson's disease (moderate-certainty evidence).
  • GLP-1RAs reduced BMI in hypothalamic obesity (moderate-certainty evidence); no significant effects in stroke or IIH.

Conclusions:

  • GLP-1RAs offer modest benefits for specific neurological conditions like Parkinson's disease motor function and hypothalamic obesity.
  • Evidence suggests no significant benefit for Alzheimer's disease cognition, stroke recovery, or IIH.
  • Further high-quality trials are needed to optimize treatment and explore mechanisms.