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

• Published in: Canadian journal of diabetes 2017-10, Vol.41 (5), p.524-535
• Main Author: Lovshin, Julie A.
• Format: Article
• Language: English
• Subjects: agonistes des récepteurs du GLP-1; cardiovascular disease; Diabetes Mellitus, Type 2 - drug therapy; diabetic nephropathy; diabète de type 2; GLP-1R agonists; Glucagon-Like Peptide-1 Receptor - agonists; Humans; Hypoglycemic Agents - therapeutic use; liraglutide; maladie cardiovasculaire; néphropathie diabétique; Prognosis; semaglutide; sémaglutide; type 2 diabetes
• ISSN: 1499-2671; 2352-3840
• DOI: 10.1016/j.jcjd.2017.08.242

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. Les options thérapeutiques actuelles du diabète de type 2 sont nombreuses; un grand nombre de classes d'antidiabétiques sont utilisées en clinique et plusieurs nouveaux médicaments candidats font l'objet d'essais cliniques de phases avancées. Cette abondance de traitement procure un avantage certain aux patients, car elle facilite la personnalisation des soins. Le positionnement fondé sur des données factuelles de ces agents constitue un défi et sous-entend qu'il faut connaître les classes de médicaments en profondeur et aussi bien les unes que les autres. La présente revue propose une mise à jour clinique sur les agonistes des récepteurs du GLP-1 (peptide-1 appar