Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis

Diabetes Care. 2008 Nov;31(11):2086-91. doi: 10.2337/dc08-1171. Epub 2008 Sep 9.


Objective: Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs.

Research design and methods: This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time.

Results: Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23-3.50) compared with current metformin use.

Conclusions: Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / chemically induced*
  • Acidosis, Lactic / epidemiology
  • Aged
  • Case-Control Studies
  • Databases, Factual / statistics & numerical data
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / adverse effects
  • Incidence
  • Male
  • Metformin / adverse effects*
  • Middle Aged
  • Odds Ratio
  • Risk Assessment
  • Sulfonylurea Compounds / adverse effects*
  • United Kingdom / epidemiology


  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Metformin