title: Antidiabetic drugs and heart failure risk in patients with type 2 diabetes in the U.K. primary care setting.
abstract: OBJECTIVE
  To assess the effects of antidiabetic drugs on the risk of heart failure in patients with type 2 diabetes.
  
  
  METHODS
  We conducted a retrospective cohort study with a newly diagnosed diabetes cohort of 25,690 patients registered in the U.K. General Practice Research Database, 1988-1999. We categorized person-time drug exposures to monotherapies in insulin, sulfonylureas (SUs), metformins, and other oral hypoglycemic agents (i.e., acarbose, guar gum) and combination therapy including insulin, combination therapy without insulin, and triple combination therapy with or without insulin. A drug-free time interval served as a reference category. Cox interval-wise (piece-wise) regression analyses were used. The main outcome was incident heart failure.
  
  
  RESULTS
  Among 43,390 drug exposure intervals for 25,690 patients who had a mean follow-up period of 2.5 years, 1,409 patients developed heart failure. Heart failure occurred most frequently in SU monotherapy exposure. After adjusting for duration of diabetes, the timing and order of treatments received, and known risk factors for heart failure, we found no differential effects among type-specific therapies. Patients with any drug use within the first year after diabetes diagnosis had a 4.75-fold higher risk (hazard ratio) for heart failure than those with drug-free status but had no increased risk during subsequent years.
  
  
  CONCLUSIONS
  In conclusion, the use of any pharmacological therapy for type 2 diabetes appears to be associated with an increased risk of heart failure. This risk does not persist beyond the first year after diagnosis of diabetes and does not appear to differ among the types of drug therapy examined. This observation suggests that the severity of diabetes or the preclinical duration of diabetes and the need for drug therapy, and not the therapy itself, is an explanation for heart failure in patients with type 2 diabetes.
authors.affiliation: Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina 27599-7075, USA.
authors.forename: Shoko
authors.initials: S
authors.lastname: Maru
authors.forename: Gary G
authors.initials: GG
authors.lastname: Koch
authors.forename: Monika
authors.initials: M
authors.lastname: Stender
authors.forename: Douglas
authors.initials: D
authors.lastname: Clark
authors.forename: Laura
authors.initials: L
authors.lastname: Gibowski
authors.forename: Hans
authors.initials: H
authors.lastname: Petri
authors.forename: Alice D
authors.initials: AD
authors.lastname: White
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Simpson
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000453:epidemiology; D005194:Family Practice; D005260:Female; D006333:Heart Failure / Q000453:epidemiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011320:Primary Health Care; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin