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Pharmacological management of type 2 diabetes: the potential of incretin-based therapies.

Abstract
Management guidelines recommend metformin as the first-line therapy for most patients with type 2 diabetes uncontrolled by diet and exercise. Efficacy with metformin therapy is usually of limited duration, which necessitates the early introduction of one or two additional oral agents or the initiation of injections, glucagon-like peptide-1 (GLP-1) agonists or insulin. Although safe and effective, metformin monotherapy has been associated with gastrointestinal side effects (≈20% of treated patients in randomized studies) and is contraindicated in patients with renal insufficiency or severe liver disease. Patients treated with a sulphonylurea are at increased risk for hypoglycaemia and moderate weight gain, whereas those receiving a thiazolidinedione are subject to an increased risk of weight gain, oedema, heart failure or fracture. Weight gain and hypoglycaemia are associated with insulin use. Thus, there is an unmet need for a safe and efficacious add-on agent after initial-therapy failure. Evidence suggests that incretin-based agents, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, can successfully achieve glycaemic targets and potentially provide cardiovascular and β-cell-function benefits. This review will examine current approaches for treating type 2 diabetes and discuss the place of incretin therapies, mainly GLP-1 agonists, in the type 2 diabetes treatment spectrum.
AuthorsB Charbonnel, B Cariou
JournalDiabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 13 Issue 2 Pg. 99-117 (Feb 2011) ISSN: 1463-1326 [Electronic] England
PMID21199262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Incretins
  • Glucagon-Like Peptide 1
  • Metformin
Topics
  • Diabetes Mellitus, Type 2 (drug therapy)
  • Dipeptidyl-Peptidase IV Inhibitors (pharmacology, therapeutic use)
  • Glucagon-Like Peptide 1 (agonists, therapeutic use)
  • Glycated Hemoglobin (drug effects)
  • Humans
  • Hypoglycemic Agents (pharmacology, therapeutic use)
  • Incretins (pharmacology, therapeutic use)
  • Metformin (pharmacology, therapeutic use)

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