Glucagon-like Peptide-1 Receptor Agonists: A Class Update for Treating Type 2 Diabetes

Sep 26, 2017Canadian journal of diabetes

Updated overview of drugs that activate GLP-1 receptors for treating type 2 diabetes

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Abstract

GLP-1 receptor agonists (GLP-1RAs) improve blood glucose control and promote weight loss without significant hypoglycemia risks.

GLP-1RAs enhance insulin secretion from pancreatic cells in response to glucose levels.
Chronic use of GLP-1RAs leads to reduced caloric intake and weight loss through appetite regulation.
Long-term use of GLP-1RAs like liraglutide and semaglutide is associated with reduced cardiovascular and renal complications in high-risk type 2 diabetes patients.
The class of GLP-1RAs has expanded to include long-acting, once-weekly formulations since 2005.
Differences in structure among GLP-1RAs may influence their therapeutic effects and safety profiles.

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Current management options for treating type 2 diabetes are diverse. Many different classes of antidiabetes therapies are used in clinic, and several new candidates are in late-phase clinical trial. This therapeutic abundance is a windfall for patients because it facilitates individualized patient care. Evidence-based positioning of these agents is challenging, however, requiring comprehensive and balanced familiarity with each drug class. In this review, I provide a clinical update of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of incretin-based, injectable antidiabetes therapies which improve fasting and postprandial blood glucose control through glucose-dependent pancreatic islet cell hormone secretion without significant risks for hypoglycemia. Chronic use of GLP-1RAs also promotes body weight loss through stimulation of GLP-1 receptors localized in hypothalamic satiety centres that regulate appetite, resulting in reduced caloric intake. Since 2005, when GLP-1RAs first received regulatory approval for type 2 diabetes, this class has expanded to include long-acting, once-weekly GLP-1RAs. Recent cardiovascular outcome trials demonstrate that long-term use of GLP-1RAs (liraglutide and semaglutide) reduce cardiovascular and renal complications of diabetes. Illustrating that GLP-1RAs are favourable in high-risk patients with type 2 diabetes. This review provides a clinical appraisal of the GLP-1RA class, highlighting intraclass similarities and differences, summarizing the clinical development of incretin-based diabetes therapies and focusing on currently approved GLP-1RAs. The review also discusses the implications of structural differences between GLP-1RA molecules and comments on the risks and benefits associated with GLP-1RAs and their positioning in treating type 2 diabetes.

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Glucagon-like Peptide-1 Receptor Agonists: A Class Update for Treating Type 2 Diabetes

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