All-cause Mortality in Diabetic Patients Treated With Combinations of Sulfonylureas and Biguanides

Diabetes Metab Res Rev. Jan-Feb 2004;20(1):44-7. doi: 10.1002/dmrr.411.


Background and aims: Increased mortality in diabetic patients treated with combinations of high doses of sulfonylureas and metformin was recently reported. This study was aimed at the assessment of mortality in patients treated with low-dose combinations of sulfonylureas and biguanides.

Methods: An observational cohort study was performed on a consecutive series of 927 outpatients with type 2 diabetes mellitus. Of these patients, 376 were treated with combinations of sulfonylureas (mean daily dose +/- SD: 7.3 +/- 3.2 mg for glibenclamide, and 338 +/- 79 mg for chlorpropamide) and biguanides (daily dose: 1.1 +/- 0.3 g for metformin, 60.1 +/- 19.6 mg for phenformin). Mortality was assessed through a search in the City of Florence Registry Office, with an average follow-up of 55.1 months.

Results: After adjusting for other potential confounders (including age, duration of diabetes, BMI, hypertension, lipid profile, HbA1c, and insulin treatment), mortality was significantly higher in patients treated with combinations of sulfonylureas and biguanides than in the rest of the sample, (relative risk, RR: 2.08; 95% confidence interval, CI 1.18-3.67, and RR: 1.68; 95%CI 1.01-2.79 among women and men, respectively).

Conclusions: A higher mortality was observed in patients treated with combinations of sulfonylureas and biguanides, even at low doses. Safety of such combinations deserves further investigation.

MeSH terms

  • Aged
  • Biguanides / therapeutic use*
  • Cause of Death
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Italy
  • Male
  • Middle Aged
  • Outpatients
  • Risk
  • Sulfonylurea Compounds / therapeutic use*


  • Biguanides
  • Hypoglycemic Agents
  • Sulfonylurea Compounds