Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination: a population-based observational study

Diabetologia. 2000 May;43(5):558-60. doi: 10.1007/s001250051343.


Aims/hypothesis: This study analysed cause-specific mortality in Type II (non-insulin-dependent) diabetic patients using either sulphonylurea alone or in combination with metformin.

Methods: Patients were followed from the first day they were taking either the combination or sulphonylurea alone. Odds ratios by Cox regression analyses were adjusted for age, sex, duration of diabetes, study area, year of inclusion and fasting blood glucose at inclusion.

Results: We included 169 patients taking sulphonylurea and metformin in combination and 741 patients taking only sulphonylurea. Mean (range) follow-up time was 6.1 (0.1-13.0) years. The adjusted odds ratio for overall mortality was 1.63 (95% confidence interval 1.27-2.09) in patients taking sulphonylurea and metformin combination vs those using sulphonylurea alone. For mortality from ischaemic heart disease and stroke the adjusted odds ratios were 1.73 (95% confidence interval 1.17-2.55) and 2.33 (95% confidence interval 1.17-4.63), respectively.

Conclusion/interpretation: There was a higher cardiovascular mortality in Type II diabetic patients taking sulphonylurea and metformin in combination than in those taking only sulphonylurea. Hence, it cannot be excluded that this kind of combination therapy possibly increases cardiovascular mortality. It is feasible that the increased mortality was secondary to a more aggressive type of diabetes in the patients using sulphonylurea and metformin in combination. Combination therapy is known to promote additional blood glucose reduction but there is as yet no evidence that a sulphonylurea and metformin combination is more beneficial on micro- or macrovascular disease than sulphonylurea or metformin alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / analysis
  • Cause of Death
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality*
  • Drug Therapy, Combination
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Metformin / administration & dosage
  • Metformin / adverse effects*
  • Myocardial Ischemia / mortality
  • Regression Analysis
  • Stroke / mortality
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / adverse effects*


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Metformin