Some antimicrobials increased admissions and ED visits for hypoglycemia in older users of glipizide or glyburide

A study of Texas Medicare patients who took either glipizide or glyburide found that those who were also prescribed clarithromycin, levofloxacin, sulfamethoxazole-trimethoprim, metronidazole, or ciprofloxacin had a much higher rate of hypoglycemic events than those taking an antibiotic not expected to interact with sulfonylureas (including azithromycin, cefdinir, cefuroxime, cephalexin, clindamycin, doxycycline, nitrofurantoin, and penicillin V).

The study was published in the October 2014 JAMA Internal Medicine, and a summary was published in the September 2014 ACP Diabetes Monthly. The following commentary by Noa Eliakim-Raz, MD, and Leonard Leibovici, MD, was published in the ACP Journal Club section of the Feb. 17, 2015, Annals of Internal Medicine.

Global prevalence of type 2 diabetes mellitus in elderly persons is increasing. Recent guidelines emphasize the avoidance of hypoglycemic episodes in older persons, even in the absence of symptoms, and recommend higher HbA1c targets than for younger adults. Randomized controlled trials often exclude frail elderly patients, who may have polypharmacy and comorbid conditions, and data are usually derived from cohort studies.

Parekh and colleagues examined the interaction between antimicrobial drugs, sulfonylureas, and risk for hypoglycemia in patients ≥ 66 years of age using Texas Medicare claims data. Bias by indication is likely: The “interacting” antibiotics are used for different indications than the “noninteracting” antibiotics. Because clinical data on infection are lacking, we cannot ascertain the link between hypoglycemia and infection. No adjustment was made for drugs other than antibiotics. Although statistically significant (due to the large numbers), the odds ratios are not large. The results are intriguing enough to warrant a prospective cohort study looking at risk factors for hypoglycemia (including antibiotics and other drugs) in older persons treated with sulfonylureas.

Should we change our practice based on the results of this study? Most of the “interacting” antibiotics are given for specific indications (if used correctly), and it is difficult to foresee alternative treatments. A heightened awareness to hypoglycemia in older patients treated with these antibiotics is warranted. We should carefully appraise the balance between potency, side effects, drug interactions, and risk for hypoglycemia when prescribing antidiabetes drugs for older patients.