Recent advances in incretin-based therapies.
The global burden of type 2 diabetes is growing. Traditional therapies are suboptimal and there is a clear unmet need for treatments that offer effective glucose control while addressing the comorbid factors associated with diabetes, such as obesity and risk of cardiovascular disease, without the fear of hypoglycaemia. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors offer a novel way of reducing hyperglycaemia by targeting the incretin system. This review provides an overview of the development of incretin-based therapies and explains their differing modes of action compared with traditional interventions. A comparison of the clinical profiles of current glucagon-like peptide-1 receptor agonists [liraglutide and exenatide (twice-daily and once-weekly)] and dipeptidyl peptidase-4 inhibitors (sitagliptin, saxagliptin, vildagliptin and linagliptin) is performed alongside a discussion of the placement of incretin-based therapies in treatment guidelines. Further improvements in this class are expected, and we will examine some of the novel glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors currently under development.
Diabetes and Endocrinology, The Royal Surrey County Hospital & University of Surrey, Guildford, UK. davidrussell-jones@nhs.net
David
D
Russell-Jones
Stephen
S
Gough
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*; D000069450:Liraglutide; D010455:Peptides / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists; D014688:Venoms / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide