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Use of Warfarin and a Sulfonylurea May Increase Hypoglycemia Risk

Retrospective study finds elevated risk with the combination in older adults

A study published in the BMJ has found that the concurrent use of warfarin plus glipizide or glimepiride increases the risk for severe hypoglycemia in older adults.

As reported by MedScape, the study population was derived from a random sample of more than 12 million Medicare fee-for-service beneficiaries ages 65 years or older from 2006 to 2011. Of those, 465,918 had type-2 diabetes and filled at least one prescription for either glipizide or glimepiride. And among those, 71,533 (15.4%) also filled a prescription for warfarin at some point during the study period.

The primary outcome was emergency-department (ED) treatment or hospital admission for hypoglycemia in a given calendar quarter ("person-quarter"). Concurrent use of warfarin and glipizide or glimepiride occurred in 9.6% of all person-quarters. Overall, ED visits and hospital admissions occurred in 0.018% of person-quarters when warfarin was used in addition to the sulfonylurea versus 0.009% of person-quarters without warfarin use. 

After adjustment for age, sex, race, and 14 chronic comorbidities, an ED visit or hospital admission for hypoglycemia was significantly more likely during the person-quarters with concurrent use of both medications, with an odds ratio (OR) of 1.22. The individual rate of hospital admission for hypoglycemia was also significantly elevated (OR, 1.45), while the individual risk for an ED visit trended toward significance (OR, 1.17).

The association was stronger during person-quarters in which a patient first used warfarin compared with subsequent use, with odds ratios of 2.47 versus 0.88, respectively (P < 0.01 for the difference).

No such associations were seen for concurrent use of warfarin and other diabetes drugs, including thiazolidinediones and insulin, or for use of glipizide/glimepiride with statins. "These analyses suggest that the observed relation between use of warfarin with glipizide/glimepiride and risk of hypoglycemia may reflect a drug–drug interaction rather than unmeasured characteristics of patients that are correlated with both warfarin use and hypoglycemia risk," Dr. John A. Romley and colleagues write.

Concurrent use of warfarin and the two sulfonylureas was also associated with an increased risk for ED visits and hospital admissions for fall-related fractures, with an adjusted OR of 1.47, and for altered consciousness/mental status (OR, 1.22). The results suggest a "substantial positive association" between concurrent use of warfarin and glipizide or glimepiride and ED visits and hospital admission for hypoglycemia and for fall-related fractures, particularly around the time that patients who are already on the sulfonylurea initiate warfarin.

Beyond just an association — which might be due to patient characteristics correlated with both warfarin use and hypoglycemia risk — the data actually point to the possibility of a significant drug interaction between the medications. "This potential interaction has not been widely appreciated, and health care professionals are not routinely alerted when patients on sulfonylureas start treatment with warfarin," Dr. Romley and colleagues write.

Close monitoring and patient education are essential for patients who require both medications, principal investigator Anne L. Peters, MD, University of Southern California (USC) professor of medicine and director of the USC Westside Center for Diabetes, told Medscape Medical News.

Asked to comment, Kasia J. Lipska, MD, an endocrinologist at Yale University in New Haven, Connecticut, who has studied hypoglycemia in the elderly, told Medscape Medical News, "I think this is an important study. … These are commonly used drugs and they frequently lead to problems that require a hospital visit. This means that we have to pay attention to them and figure out how to make prescribing safer."

Source: Medscape, December 21, 2015; BMJ, December 7, 2015.

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