Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database

BMJ. 2009 Dec 3;339:b4731. doi: 10.1136/bmj.b4731.


Objective: To investigate the risk of incident myocardial infarction, congestive heart failure, and all cause mortality associated with prescription of oral antidiabetes drugs.

Design: Retrospective cohort study.

Setting: UK general practice research database, 1990-2005.

Participants: 91,521 people with diabetes.

Main outcome measures: Incident myocardial infarction, congestive heart failure, and all cause mortality. Person time intervals for drug treatment were categorised by drug class, excluding non-drug intervals and intervals for insulin.

Results: 3588 incident cases of myocardial infarction, 6900 of congestive heart failure, and 18,548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P<0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P<0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P=0.02 to P<0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P=0.14 to P=0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded.

Conclusions: Our findings suggest a relatively unfavourable risk profile of sulphonylureas compared with metformin for all outcomes examined. Pioglitazone was associated with reduced all cause mortality compared with metformin. Pioglitazone also had a favourable risk profile compared with rosiglitazone; although this requires replication in other studies, it may have implications for prescribing within this class of drugs.

Publication types

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

MeSH terms

  • Administration, Oral
  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetic Angiopathies / chemically induced*
  • Diabetic Angiopathies / mortality
  • Female
  • Fractures, Bone / chemically induced
  • Heart Failure / chemically induced*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Male
  • Metformin / administration & dosage
  • Metformin / adverse effects
  • Middle Aged
  • Myocardial Infarction / chemically induced*
  • Myocardial Infarction / mortality
  • Pioglitazone
  • Retrospective Studies
  • Risk Factors
  • Rosiglitazone
  • Sulfonylurea Compounds / administration & dosage*
  • Sulfonylurea Compounds / adverse effects
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / adverse effects


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