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Warfarin with Sulfonylurea Increases Risk of Hypoglycemia Events

National cohort study examined events in Medicare beneficiaries.

The geriatric population in the United States continues to grow as medical technology advances. National surveillance studies found that the elderly population is twice as likely to experience adverse drug events due to greater use and renal impairment. In the U.S., almost 100,000 elderly patients are admitted to hospitals for adverse drug events, allergic reactions, or drug overdose. Over 40% of these admissions are related to hypoglycemia agents or warfarin. Warfarin is an anticoagulant that reduces the formation of blood clots, which prevents the occurrence of heart attacks, strokes, and blood clots in veins and arteries. Sulfonylurea are a class of antidiabetic drugs that increases insulin release by acting on the beta cells found in the pancreas. It has been known that warfarin may potentially increase the hypoglycemic effects of sulfonylureas, however, no large studies have ever been conducted to support this theory.

A recent study by the National Institute on Aging and the University of Southern California investigated the association of warfarin use and increased risk of hypoglycemic events among elderly patients. The study was a retrospective cohort of pharmacy and medical claims from Medicare beneficiaries between 2006 and 2011. The study randomly selected 20% of Medicare patients 65 years or older who have filled a prescription for glipizide or glimepiride and warfarin. The study’s primary outcome looked at emergency department visits or hospital admissions with a primary diagnosis of hypoglycemia. Of the 465,918 fees sampled, there were 71,533 (15.4%) samples that used warfarin at some point during the study period.

The results of the study found that hospital admissions or emergency department visits for hypoglycemia were more common in patients with concurrent warfarin use than those without warfarin use (odds ratio 1.22). The study found that those on warfarin are older, more likely to be male and white, and have higher rates of chronic comorbidities such as hypertension. The association between warfarin use and sulfonylurea was strongest in people using warfarin for the first time. The data from the study also looked at hypoglycemia in patients on concurrent statin use, but found no association. The study results supports the drug interaction between warfarin and sulfonylurea noted in clinical drug databases.

What this study adds is a substantial positive association between use of warfarin with glipizide/glimepiride and hospital admission/emergency department visits for hypoglycemia and related diagnoses, particularly in patients starting warfarin. The findings suggest the possibility of a significant drug interaction between these medications.

The implication of this study also suggests the need for increased care in patients on warfarin and sulfonylureas. Patients should be advised to monitor their blood glucose more frequently while on the medication.  Medication therapy management services may play a major role in patient care. These services focus directly on evaluation and assessment of a patient’s therapy and can directly interact with patients. The role of MTM can reduce the financial burden of healthcare on both patient and society. Reducing hospital admission and length of stay at the hospital, which averages $20,500 per day, can provide substantial cost savings.

In conclusion, there is evidence suggesting that concurrent use of warfarin and sulfonylurea puts patients at an increased risk of hypoglycemia resulting in hospital admission or hospitalization. Greater care should be taken with these patients to advise them on the potential hazards and offer education to reduce their risk. These patients should be monitored more closely to reduce their risk of hypoglycemia and improve their quality of care. The study found that patients starting on warfarin are at the highest risk of hypoglycemia. Patient education and healthcare services like MTM can reduce a patient’s risk of hypoglycemia as well as reduce healthcare cost burden on the patient and society.

Practice Pearls:

  • Antidiabetic drugs and anticoagulant drugs account for 40% of hospital admission for patients over 65 years old.
  • Evidence supports that warfarin, when taken with sulfonylureas, may increase the risk of hypoglycemia in patients with type 2 diabetes.
  • Healthcare providers should be aware of this risk between warfarin and sulfonylurea to better educate patients as well as monitor them closely.

Romley, John A., et al. “Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis.” BMJ 351 (2015): h6223.

National Center for Health Statistics. Health, United States, 2013: with special feature on prescription drugs. NCHS, 2014

Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. National surveillance of emergency department visits for outpatient adverse drug events.JAMA2006;296:1858-66.