title: Extra-pancreatic effects of incretin-based therapies: potential benefit for cardiovascular-risk management in type 2 diabetes.
abstract: Development of cardiovascular disease is one of the major complications of type 2 diabetes mellitus (T2DM). The chronic hyperglycaemic state is often accompanied by dyslipidaemia, hypertension, low-grade systemic inflammation and oxidative stress which collectively result in a high risk of micro- and macrovascular complications. Current glucose-lowering agents do not sufficiently address fore-mentioned macrovascular-risk factors. Recently, new therapeutic agents were introduced, based on the incretin hormone glucagon-like peptide-1 (GLP-1), that is, the GLP-1 receptor agonists (GLP-1RA) and dipeptidyl-peptidase 4 (DPP-4) inhibitors. Beside its effect on pancreatic insulin secretion, GLP-1 exerts several extra-pancreatic effects such as slowing down gastric emptying, promoting satiety and reducing food intake and weight loss. Also, GLP-1 and GLP-1RA were shown to improve cardiovascular-risk profiles, by reducing body fat content, blood pressure, circulating lipids and inflammatory markers in patients with T2DM. This review summarizes the presently known evidence with regard to extra-pancreatic effects of the incretin-based agents, focusing on the actions that improve the cardiovascular-risk profile. We present available data from clinical trials of at least 24 week duration, but also findings from small-sized clinical 'proof of principle' studies. We conclude that GLP-1 RA and to a lesser extent DPP-4 inhibitors are promising agents with regard to their effects on body weight, blood pressure and lipids, which collectively ameliorate the cardiovascular-risk profile and as such may have added value in the treatment of T2DM. However, large-sized long-term outcome studies are warranted to show the true added value of these agents in the treatment of patients with T2DM.
authors.affiliation: Department of Internal Medicine, Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands. r.vangenugten@vumc.nl
authors.forename: R E
authors.initials: RE
authors.lastname: van Genugten
authors.forename: D L
authors.initials: DL
authors.lastname: Möller-Goede
authors.forename: D H
authors.initials: DH
authors.lastname: van Raalte
authors.forename: M
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000517:prevention & control; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000517:prevention & control; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D000067757:Glucagon-Like Peptide-1 Receptor; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000819:agonists / Q000627:therapeutic use*; D054795:Incretins / Q000819:agonists / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000819:agonists; D012307:Risk Factors
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D018027:Receptors, Glucagon