Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia

A nested case-control analysis

BODMER, MICHAEL MD, MSC
MEIER, CHRISTIAN MD
KRÄHENBÜHL, STEPHAN MD, PHD
JICK, SUSAN S. DSC
MEIER, CHRISTOPH R. PHD, MSC

From the ¹Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland; the ²Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Basel, Basel, Switzerland; the ³Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts; the ⁴Department of Epidemiology, School of Public Health, Boston University, Massachusetts; and the ⁵Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland.

Corresponding author: Christoph R. Meier, [email protected]

Published ahead of print at http://care.diabetesjournals.org on 9 September 2008.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

Received 27 June 2008 and accepted 10 August 2008

Diabetes Care 31(11):p 2086-2091, November 2008.

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.