Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

Diabetologia. 2006 May;49(5):930-6. doi: 10.1007/s00125-006-0176-9. Epub 2006 Mar 9.


Aims/hypothesis: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin.

Subjects and methods: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group.

Results: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA(1c), smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality.

Conclusions/interpretation: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Blood Pressure
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / mortality*
  • Diabetic Angiopathies / physiopathology
  • Drug Therapy, Combination
  • Female
  • Hospitalization
  • Humans
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Scotland / epidemiology
  • Sulfonylurea Compounds / therapeutic use*
  • Survival Analysis


  • Sulfonylurea Compounds
  • Metformin