Original ResearchThe Hypoglycemic Risk of Glyburide (Glibenclamide) Compared with Modified-Release Gliclazide
Introduction
Sulfonylureas are easy to administer, low in cost and, through their insulin-secreting mechanism, are among the most potent of all oral hypoglycemic agents 1, 2 These drugs, however, must be used very carefully in older adults to avoid hypoglycemia because this population commonly has medical comorbidities, takes multiple medications and has altered drug metabolism.
In Canada, glyburide (glibenclamide) and gliclazide are 2 commonly prescribed sulfonylureas. Because of glyburide’s high affinity for the sulfonylurea receptor (3), its long duration of action and its glucose-lowering metabolites (4), the risk for hypoglycemia with glyburide is anticipated to be higher than that with other sulfonylureas 5, 6, 7. Accordingly, diabetes guidelines have cautioned against the use of glyburide when treating older persons in favour of other oral hypoglycemic agents (8). However, to our knowledge, the risk for hypoglycemia when using glyburide compared with a long-acting alternative, modified-release gliclazide (9), has not been examined in a large representative population of older adults in routine practice. For this reason, we conducted 2 population-based cohort studies to examine the risk of hospital encounters with hypoglycemia after the initiation of glyburide vs. once-daily modified-release gliclazide in the outpatient setting.
Section snippets
Study design and setting
We conducted 2 population-based matched retrospective cohort studies of older adults using linked healthcare databases in Ontario, Canada. Ontario has approximately 1.8 million adults aged 65 years or older who have comprehensive universal healthcare, including coverage for outpatient prescription medications, physician services, hospitalizations and diagnostic testing (10). The reporting of these studies follows guidelines for observational studies (Appendix Table A1) (11).
The studies were
Baseline characteristics
We identified 18 804 patients who had been prescribed glyburide (n=13 550) or gliclazide (n=5254). Baseline characteristics of the 2 groups before and after matching are presented in Table 1, and the characteristics of patients with and without laboratory values available in the year prior are illustrated in Appendix Table A4. After matching, we retained 4374 patients in each group, and baseline characteristics were similar in the groups. Over the course of the study, there were 4288 unique
Principal findings and main implications
Despite cautionary guidelines, glyburide continues to be initiated in older adults in routine care (8). Yet long-acting modified-release gliclazide is more convenient for patients (once a day) than the many glyburide dosing regimens. When prescribed as monotherapy or in the presence of metformin, modified-release gliclazide is a safer sulfonylurea than glyburide and is associated with less hypoglycemia. Although modified-release gliclazide has a long duration of action, its hypoglycemia risk
Conclusions
Although glyburide is effective in lowering blood glucose in patients with diabetes, its use in older adults is associated with a much higher risk for hypoglycemia than is modified-release gliclazide. The results of our studies may help to convince physicians, pharmacists and patients who still use glyburide to consider modified-release gliclazide a more convenient and safer alternative.
Acknowledgements
We thank Brogan Inc, Ottawa, for use of its drug product and therapeutic class database. We thank Gamma Dynacare for the use of their outpatient laboratory database and the team at London Health Sciences Centre, St Joseph’s Health Care and the Thames Valley Hospitals for providing access to the Cerner laboratory database. We thank Salimah Shariff, PhD (from ICES Western in London, Canada) for administrative support.
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