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

Abstract

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 mellitus using oral antidiabetic drugs.

Research Design and Methods: Nested case-control analysis using the UK-based General Practice Research Database to identify patients with type 2 diabetes mellitus who used oral antidiabetic drugs. Within the study population all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia cases matched up to four control patients to these cases on age, sex, practice, and calendar time.

Results: Among the study population of 50,048 type 2 diabetics, 6 cases of lactic acidosis during current use of oral antidiabetics 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 cases.

Results: 2,025 cases of hypoglycemia and 7,278 matched controls were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted OR for current use of sulfonylureas was 2.79 (95% CI 2.23 to 3.50) as compared with current metformin use.

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