A Systematic Review and Meta-Analysis of Hypoglycemia and Cardiovascular Events

A comparison of glyburide with other secretagogues and with insulin

  1. Azim S. Gangji, MD, FRCPC12,
  2. Tali Cukierman, MD23,
  3. Hertzel C. Gerstein, MD, FRCPC23,
  4. Charles H. Goldsmith, PHD2 and
  5. Catherine M. Clase, MB, FRCPC12
  1. 1Division of Nephrology, McMaster University and St. Joseph’s Healthcare, Hamilton, Ontario, Canada
  2. 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
  3. 3Division of Endocrinology & Metabolism and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
  1. Address correspondence and reprint requests to Catherine M. Clase, 708-25 Charlton Ave. East, Hamilton, Ontario L8P 3P7, Canada. E-mail: clase{at}mcmaster.ca


OBJECTIVE—Glyburide is the most widely used sulfonylurea but has unique pharmacodynamic properties that may increase harm. We hypothesized that glyburide causes more hypoglycemia and cardiovascular events than other secretagogues or insulin.

RESEARCH DESIGN AND METHODS—Data sources were Medline, Embase, Cochrane, and three other web-based clinical trial registers (1966–2005). Parallel, randomized, controlled trials in people with type 2 diabetes comparing glyburide monotherapy with monotherapy using secretagogues or insulin were selected. Outcomes were hypoglycemia, glycemic control, cardiovascular events, body weight, and death. Titles and abstracts of 1,806 publications were reviewed in duplicate and 21 relevant articles identified. Data on patient characteristics, interventions, outcomes, and validity were extracted in duplicate using predefined criteria.

RESULTS—Glyburide was associated with a 52% greater risk of experiencing at least one episode of hypoglycemia compared with other secretagogues (relative risk 1.52 [95% CI 1.21–1.92]) and with 83% greater risk compared with other sulfonylureas (1.83 [1.35–2.49]). Glyburide was not associated with an increased risk of cardiovascular events (0.84 [0.56–1.26]), death (0.87 [0.70–1.07]), or end-of-trial weight (weighted mean difference 1.69 kg [95% CI −0.41 to 3.80]) compared with other secretagogues. Limitations included suboptimal reporting of original trials. Loss to follow-up exceeded 20% in some studies, and major hypoglycemia was infrequently reported.

CONCLUSIONS—Glyburide caused more hypoglycemia than other secretagogues and other sulfonylureas. Glyburide was not associated with an increased risk of cardiovascular events, death, or weight gain.


  • Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc06-1789.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    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.

    • Accepted November 12, 2006.
    • Received August 23, 2006.
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