, Volume 17, Issue 3, pp 333–350 | Cite as

Clinical pharmacology of glucagon-like peptide-1 receptor agonists

  • Dimitrios Sfairopoulos
  • Stavros Liatis
  • Stelios Tigas
  • Evangelos Liberopoulos
Review Article


Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an important asset in the armamentarium for the treatment of type 2 diabetes mellitus (type 2 DM). Incretin failure is a critical etiopathogenetic feature of type 2 DM, which, if reversed, results in improved glycaemic control. GLP-1 RAs are injectable peptides that resemble the structure and function of endogenous incretin GLP-1, but as they are not deactivated by the dipeptidyl peptidase-4 (DPP-4), their half-life is prolonged compared with native GLP-1. Based on their ability to activate GLP-1 receptor, GLP-1 RAs are classified as short-acting (exenatide twice-daily and lixisenatide once-daily), and long-acting (liraglutide once-daily and the once-weekly formulations of exenatide extended-release, dulaglutide, and albiglutide). Semaglutide, another long-acting, once-weekly GLP-1 RA, was recently approved by the FDA and EMA. Although all of these agents potently reduce haemoglobin A1C (HbA1c), there are unique features and fundamental differences among them related to fasting and postprandial hyperglycaemia reduction, weight loss potency, cardiovascular protection efficacy, and adverse events profile. It is imperative that current evidence be integrated and applied in the context of an individualised patient-centred approach. This should include not only glucose management but also targeting as many as possible of the pathophysiologic mechanisms responsible for type 2 DM development and progression.


GLP-1 receptor agonists Type 2 diabetes Exenatide Liraglutide Dulaglutide Semaglutide 


Compliance with ethical standards

Conflict of interest

DS has no relevant conflict of interest to report. SL has received research support and/or consulting honoraria from Astra-Zeneca, Boehringer-Ingelheim, MSD, Novartis, Novo Nordisk, Sanofi-Aventis, Eli Lilly, and ELPEN. ST has received lecture honoraria or travel grants from, and/or has participated in advisory boards of, Astra-Zeneca, Boehringer-Ingelheim, Eli Lilly, ELPEN, Galenica, MSD, Novartis, Novo Nordisk, and Sanofi-Aventis. EL has participated in educational, research, and advisory activities sponsored by Astra-Zeneca, MSD, Eli Lilly, Bayer, Amgen, Sanofi-Aventis, Boehringer-Ingelheim, Novartis, Novo Nordisk, Servier, Galenica, ELPEN, and Valeant.


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Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  • Dimitrios Sfairopoulos
    • 1
  • Stavros Liatis
    • 2
  • Stelios Tigas
    • 3
  • Evangelos Liberopoulos
    • 1
  1. 1.Department of Internal Medicine, School of MedicineUniversity of IoanninaIoanninaGreece
  2. 2.First Department of Propaedeutic and Internal Medicine, Medical School, Laiko General HospitalNational and Kapodistrian University of AthensAthensGreece
  3. 3.Department of Endocrinology, School of MedicineUniversity of IoanninaIoanninaGreece

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