Ciprofloxacin and Risk of Hypoglycemia in Non-diabetic Patients

Abiel Berhe; Mulugeta Russom; Fithawit Bahran; Goitom Hagos

Disclosures

J Med Case Reports. 2019;13(142) 

In This Article

Discussion

Unlike other fluoroquinolones, the association of ciprofloxacin and hypoglycemia in patients without diabetes is not well documented, and studies conducted previously did not show a statistically significant association.[6,7] This study, however, found a suggestive causal association between ciprofloxacin and hypoglycemia in patients without diabetes, which strengthens the FDA recommendation provided in July 2018.[10] The facts that the majority of cases were reported from different geographical areas, the temporal relationship was plausible, and hypoglycemia was encountered in a substantial number of cases solely after administration of ciprofloxacin support a causal association. Besides, the positive de-challenge and rechallenge documented in some cases and the specificity of the association support the causation.

Two experimental studies in rat islet cells exposed to quinolones showed an increase in insulin secretion via blockade of adenosine triphosphate (ATP)–dependent potassium channels.[21,22] Thus, the possible mechanism that explains the causal association of ciprofloxacin and hypoglycemia could be increased insulin release via blockade of ATP-sensitive potassium channels in the beta-cells of the pancreas. Other experimental studies using rat islet cells also suggest that fluoroquinolones act not as initiators but as augmenters of stimulated insulin release from these cells,[23] which might be a reason that the majority of the episodes of hypoglycemia in our patient were occurring postprandially. Although ciprofloxacin is known to inhibit CYP1A4 isoenzymes that lead to drug interactions, especially with diabetic drugs such as glyburide,[24] none of our cases were taking diabetic drugs, and ciprofloxacin was the sole drug used in about half of them.

The availability of the plausible biological mechanism, existence of experimental evidence, analogy, coherence, and reversibility of hypoglycemia in a majority of the cases following withdrawal of ciprofloxacin are also elements that support a causal relationship between ciprofloxacin and hypoglycemia.

Because the cases were voluntarily reported from different parts of the world, we cannot estimate the incidence rate of hypoglycemia associated with ciprofloxacin, which is the inherent limitation of spontaneous reporting of adverse drug reactions. Another limitation of this study is that insulin level was not determined, and because there was not any coreported diabetic drugs in the 35 cases, we assumed that the patients were not diabetic, which could also lead to exposure misclassification bias. Moreover, although a substantial number of the events were marked as "serious," we do not know the degree, duration, and/or reversibility of hypoglycemia in some of the cases.

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