title: Cardiovascular Effects of Incretin-Based Therapies.
abstract: The incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs, are important new classes of therapy for type 2 diabetes mellitus (T2DM). These agents prolong the action of the incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), by inhibiting their breakdown. The incretin hormones improve glycemic control in T2DM by increasing insulin secretion and suppressing glucagon levels. The cardiovascular (CV) effects of the incretin-based therapies have been of substantial interest since 2008, when the US Food and Drug Administration began to require that all new therapies for diabetes undergo rigorous assessment of CV safety through large-scale CV outcome trials. This article reviews the most recent CV outcome trials of the DPP-4 inhibitors (SAVOR-TIMI 53, EXAMINE, and TECOS) as evidence that the incretin-based therapies have acceptable CV safety profiles for patients with T2DM. The studies differ with regard to patient population, trial duration, and heart failure outcomes but show similar findings for CV death, nonfatal myocardial infarction, and stroke, as well as hospitalization for unstable angina.
authors.affiliation: Division of Hypertension and Clinical Pharmacology, Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut 06032; email: wwhite@uchc.edu.
authors.forename: William B
authors.initials: WB
authors.lastname: White
authors.affiliation: University of Connecticut School of Pharmacy, Storrs, Connecticut 06269; email: william.baker_jr@uconn.edu.
authors.forename: William L
authors.initials: WL
authors.lastname: Baker
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives; D002318:Cardiovascular Diseases / Q000150:complications*; D002319:Cardiovascular System / Q000187:drug effects*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004151:Dipeptides / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000494:pharmacology*; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054795:Incretins / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D010880:Piperidines / Q000009:adverse effects; D000068900:Sitagliptin Phosphate / Q000009:adverse effects; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D010880:Piperidines; D014498:Uracil; D052216:Glucagon-Like Peptide 1; C502994:saxagliptin; C520853:alogliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate
keywords: cardiovascular safety outcome trials; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide; type 2 diabetes mellitus