Coronary heart disease outcomes in patients receiving antidiabetic agents in the PharMetrics database 2000-2007

Pharmacoepidemiol Drug Saf. 2008 Aug;17(8):760-8. doi: 10.1002/pds.1598.


Background: The risk of coronary heart disease (CHD) in users of antidiabetic agents must be quantified to permit reasoned therapeutic choices.

Objectives: To assess the risk of myocardial infarction (MI) and coronary revascularization (CR), in diabetic patients who began rosiglitazone, pioglitazone, metformin, or sulfonylureas.

Methods: We conducted a retrospective cohort study of MI and CR in the PharMetrics database. We performed head-to-head comparisons using propensity-score-stratified Cox proportional hazards models, examining risks both on-treatment and during total follow-up before regimen switches.

Results: For the combined outcome (MI and CR), the crude rates per 1000 person years were 9 on monotherapy, 13 on dual therapy, and 21 on therapies combined with insulin. In the absence of insulin, regimens containing thiazolidinediones (TZDs) tended toward lower risk than comparable regimens containing sulfonylureas and higher risk than those containing metformin. The summary hazard ratio for rosiglitazone versus pioglitazone was 1.04 (95%CI: 0.94-1.14) for total follow-up and 1.05 (0.92-1.19) for on-treatment time. For MI, the hazard ratios were 1.07 (0.89-1.27) for total follow-up and 1.21 (0.95-1.54) for on-treatment time.

Conclusions: The present data indicate that the risk of CHD in patients using TZDs appears to lie between the risks associated with sulfonylureas and metformin. Neither the risk of MI and CR together nor the risk of MI alone was significantly different between rosiglitazone and pioglitazone. A nonsignificant observed excess risk of 21% for MI during on-treatment time will require combination with the results of other studies to provide a reliable assessment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Coronary Disease / chemically induced*
  • Coronary Disease / prevention & control*
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Metformin / pharmacology
  • Myocardial Infarction
  • Outcome Assessment, Health Care
  • Pioglitazone
  • Risk Factors
  • Rosiglitazone
  • Sulfonylurea Compounds / pharmacology
  • Thiazolidinediones / pharmacology


  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Rosiglitazone
  • Metformin
  • Pioglitazone