title: Risk of cardiovascular disease: the effects of diabetes and anti-diabetic drugs - a nested case-control study.
abstract: OBJECTIVE
  Type 2 diabetes (DM) increases the risk of cardiovascular disease. We investigated the effects of antidiabetic drugs on the composite endpoint (CE) of ischemic heart disease, heart failure or stroke in DM patients.
  
  
  METHODS
  We conducted a nested case-control study. Cases were DM patients who subsequently suffered from CE; controls were DM patients with no history of CE after DM diagnosis. Using the Danish National Hospital Discharge Register, we included DM patients with information on date of DM diagnosis, date of CE, and comorbidities. From the Central Region of Jutland, Denmark, medication use and biochemical parameters were collected. Logistic regression analyses were conducted and mutually adjusted for comorbidities, pharmaceutical use, and biochemical parameters.
  
  
  RESULTS
  10,073 DM patients were included (65,550person-years). 1947 suffered from a subsequent CE. CE prior to DM diagnosis (OR=20.18, 95% CI: 16.88-24.12), neuropathy (OR=1.39, 95% CI: 1.05-1.85) and peripheral artery disease (OR=1.31, 95% CI: 1.02-1.69) increased the risk of CE. Biguanides (OR=0.62 95% CI; 0.54-0.71) and liraglutide (OR=0.48 95% CI; 0.38-0.62) significantly decreased the risk of CE as did statin treatment (OR=0.63, 95% CI: 0.54-0.72). DPP-4 inhibitors, insulin and β-cell stimulating agents had neutral effect. When results were adjusted for biochemical risk markers (1103 patients, 7271person-years, 189 cases), biguanides (OR=0.54, 95% CI: 0.34-0.87) and liraglutide (OR=0.32, 95% CI: 0.14-0.70) treatment retained a significant risk reduction. The effect of liraglutide was dose and duration dependent (p<0.05).
  
  
  CONCLUSIONS
  We have shown an association between the use of biguanides and liraglutide and a reduced risk of CE in DM patients.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark; Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia; Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Aarhus, Denmark; Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark. Electronic address: mg@farm.au.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Gejl
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Starup-Linde
authors.affiliation: Department of Neurology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Scheel-Thomsen
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Soeren
authors.initials: S
authors.lastname: Gregersen
authors.affiliation: Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents
keywords: Biguanides; Cardiovascular disease; GLP-1; Glucagon-like peptide-1; Liraglutide; Type 2 diabetes mellitus