title: The association of the treatment with glucagon-like peptide-1 receptor agonist exenatide or insulin with cardiovascular outcomes in patients with type 2 diabetes: a retrospective observational study.
abstract: BACKGROUND
  To evaluate the association of treatment with glucagon-like peptide-1 (GLP-1) receptor agonist exenatide and/or insulin on macrovascular outcomes in patients with type 2 diabetes (T2DM).
  
  
  METHODS
  We conducted a retrospective longitudinal pharmaco-epidemiological study using large ambulatory care data to evaluate the risks of heart failure (HF), myocardial infarction (MI) and stroke in established T2DM patients who received a first prescription of exenatide twice daily (EBID) or insulin between June 2005 and May 2009, with follow-up data available until December 2012. Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870). Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
  
  
  RESULTS
  During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1). Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).
  
  
  CONCLUSIONS
  Treatment with exenatide, with or without concomitant insulin was associated with reduced macrovascular risks compared to insulin; although inherent potential bias in epidemiological studies should be considered.
authors.affiliation: Clinical Trials & Biostatistics Unit, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Brisbane, Australia. sanjoy.paul@qimrberghofer.edu.au.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Paul
authors.affiliation: Clinical Trials & Biostatistics Unit, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, 4006, Brisbane, Australia. kerenaftali.klein@qimrberghofer.edu.au.|Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia. kerenaftali.klein@qimrberghofer.edu.au.
authors.forename: Kerenaftali
authors.initials: K
authors.lastname: Klein
authors.affiliation: Bristol-Myers Squibb, San Diego, CA, USA. dmaggs@gidynamics.com.
authors.forename: David
authors.initials: D
authors.lastname: Maggs
authors.affiliation: University of Washington, Seattle, WA, USA. bestj@uw.edu.
authors.forename: Jennie H
authors.initials: JH
authors.lastname: Best
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists