Coronary Heart Disease Outcomes in Patients Receiving Antidiabetic Agents

Pharmacoepidemiol Drug Saf. 2007 Jul;16(7):711-25. doi: 10.1002/pds.1443.


Background: There is conflicting evidence on the reduction of cardiovascular risk in diabetic patients treated with oral antidiabetic agents.

Objectives: To compare the risk of myocardial infarction (MI) and coronary revascularization (CR) in type 2 diabetic patients treated with rosiglitazone, metformin, or sulfonylurea.

Methods: Using data from a large US insurer, we created propensity-matched cohorts. We identified hospitalizations for MI or CR. We calculated incidence rates and 95% confidence intervals for the outcomes and estimated risks from Cox proportional hazards models.

Results: We identified 26,931 initiators of monotherapy, 4,086 initiators of dual-therapy, and 2,346 initiators of combination with insulin therapy. There was no difference between the risk of the composite outcome with rosiglitazone monotherapy compared to metformin monotherapy (HR 1.07, 95% CI: 0.85, 1.34), and similarly with rosiglitazone monotherapy compared to sulfonylurea monotherapy (HR 0.82, 95% CI: 0.67, 1.02). There was no difference in the risk of outcome with rosiglitazone in combination with insulin therapy compared to other oral antidiabetic agents in combination with insulin (HR 0.88, 95% CI: 0.59, 1.32). Overall, there was little difference in the risk of the composite outcome or of the individual outcomes of MI and CR comparing rosiglitazone therapies to non-rosiglitazone therapies (HR for composite outcome 0.93, 95% CI: 0.80, 1.10).

Conclusions: The results from the monotherapy and the dual-therapy comparisons, though not individually significant, are consistent in suggesting that the risk of cardiovascular outcome events in patients using rosiglitazone may lie between the risks associated with sulfonylureas (higher incidence) and metformin (lower incidence).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use*
  • Incidence
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Myocardial Revascularization / statistics & numerical data*
  • Retrospective Studies
  • Risk Factors
  • Rosiglitazone
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome
  • United States / epidemiology


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