title: Investigational insulin secretagogues for type 2 diabetes.
abstract: BACKGROUND
  Insulin secretory defects are a key feature in the pathophysiology of type 2 diabetes (T2D). Classical insulin-secreting agents such as sulfonlyureas stimulate insulin secretion independent of glucose and cause hypoglycemia. Despite the advantages offered by incretin-based therapies, there is still a medical need for developing new insulin secretagogues for treating T2D.
  
  
  METHODS
  This article discusses: the new advances in the field of incretin-based therapies, glucokinase (GK) activators, free fatty acid receptor (FFAR) or G protein-coupled receptor (GPR) agonists (GPR40, GPR119, GPR120), imeglimin and some other insulin secretagogues with diverse mechanisms of action still in preclinical development.
  
  
  CONCLUSIONS
  New insulin secretagogues should offer major advantages over sulfonylureas and gliptins. The challenge is to avoid uncontrolled insulin secretion and minimize the risk of hypoglycemia, to protect cells from progressive loss of mass and function for a better durability of glucose control, and to offer a good safety profile. Numerous approaches are in development. However, it is too early to decide whether one new pharmacological class will emerge as a clinically useful insulin secretagogue in the near feature.
authors.affiliation: a Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM) , University of Liège , Liège , Belgium.|b Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine , CHU , Liège , Belgium.
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D005941:Glucokinase / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D015507:Drugs, Investigational; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D026902:Potassium Channel Blockers; D043562:Receptors, G-Protein-Coupled; D005941:Glucokinase
keywords: Beta cell; GPR agonist; glucokinase activator; imeglimin; incretin; insulin secretion; type 2 diabetes