What is a Glucagon-like peptide (GLP) receptor antagonist?

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Last updated: May 7, 2025View editorial policy

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From the Guidelines

GLP receptor antagonists have limited therapeutic applications in current clinical practice, and their use is primarily as research tools to understand GLP-1 physiology. The most well-known GLP receptor antagonist is exendin-(9-39), which works by preventing natural GLP-1 from binding to its receptors, thereby increasing glucagon secretion and blood glucose levels 1. This mechanism makes them potentially useful for treating conditions like hypoglycemia, particularly in conditions such as congenital hyperinsulinism or post-bariatric hypoglycemia.

Key Points

  • GLP receptor antagonists are not widely used in clinical practice due to their limited therapeutic applications
  • Exendin-(9-39) is the most well-known GLP receptor antagonist, primarily used as a research tool
  • The typical dosing of exendin-(9-39) in research settings is 300-600 pmol/kg/min administered intravenously, though this varies by study protocol 1
  • These compounds help researchers understand GLP-1 physiology and may eventually lead to treatments for conditions characterized by excessive insulin secretion

Potential Uses

  • Treating hypoglycemia, particularly in conditions such as congenital hyperinsulinism or post-bariatric hypoglycemia
  • Understanding GLP-1 physiology and its role in glucose metabolism
  • Potential future treatments for conditions characterized by excessive insulin secretion

Current Status

  • GLP receptor antagonists remain primarily investigational tools rather than approved medications
  • Further research is needed to fully understand their potential therapeutic applications and to develop them into clinically useful treatments 1

From the Research

GLP Receptor Antagonist

  • There is no direct information available on GLP receptor antagonists in the provided studies, as they primarily focus on GLP-1 receptor agonists (GLP-1 RAs) and their role in treating type 2 diabetes and other conditions 2, 3, 4, 5, 6.
  • The studies discuss the mechanisms of action, effectiveness, and potential side effects of GLP-1 RAs, but do not mention GLP receptor antagonists specifically.
  • GLP-1 RAs are known to have various benefits, including improving glycemic control, promoting weight loss, and reducing the risk of cardiovascular events 2, 3, 4, 5, 6.
  • However, without direct information on GLP receptor antagonists, it is not possible to provide a detailed analysis of their effects or potential uses.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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