Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis

Abstract

ABSTRACTwhat thiS Study addS A substantial positive association was seen 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.

Serious Hypoglycemia and Use of Warfarin in Combination With Sulfonylureas or Metformin

“…We found that the RR for the association between warfarin and serious hypoglycemia across all temporal risk windows combined was statistically elevated in users of glimepiride and in users of metformin, and nearly so in users of glipizide. In a prior study, warfarin use was associated with an elevated risk of serious hypoglycemia in users of either glipizide or glimepiride (odds ratio for both sulfonylureas considered collectively, 1.22; 95% CI, 1.05–1.42) and a similar, nearly statistically significantly elevated odds ratio in users of metformin . In the present study, the association between warfarin and serious hypoglycemia appeared to be strongest after 120 days of concomitant use of warfarin with most of the antidiabetes drugs examined, including metformin.…”

“…The increased rate of serious hypoglycemia with warfarin observed in users of metformin (which we had originally included as a negative control object drug) supports a previously hypothesized hypoglycemic effect of warfarin. It also suggests that the increased risk might be attributable primarily to a hypoglycemic effect of warfarin itself, rather than to a drug interaction between warfarin and either sulfonylureas or metformin, considering that the magnitude of the elevated risk was similar between sulfonylureas and metformin in both the current study and the earlier study . Further research is needed to better understand underlying mechanisms.…”

“…In a prior study, warfarin use was associated with an elevated risk of serious hypoglycemia in users of either glipizide or glimepiride (odds ratio for both sulfonylureas considered collectively, 1.22; 95% CI, 1.05-1.42) and a similar, nearly statistically significantly elevated odds ratio in users of metformin. 17 In the present study, the association between warfarin and serious hypoglycemia appeared to be strongest after 120 days of concomitant use of warfarin with most of the antidiabetes drugs examined, including metformin. Given the lack of known pharmacokinetic or pharmacodynamic mechanisms by which warfarin could interact with metformin (which itself is associated with a low risk of hypoglycemia 18 ) to increase the risk of hypoglycemia, what could explain these findings?…”

An evidence-based perspective on warfarin and the growing skeleton

“…Furthermore, a recent population-based study reported that atrial fibrillation was linked to the increased risk of fractures that could be reversed by warfarin therapy [11]. In contrast, one exceptional case might be type 2 diabetes patients treated with glipizide or glimepiride; there appears to be the increased risk of fall-related fractures resulting from hypoglycemia associated with the interaction of warfarin and sulfonylureas [12][13][14].…”

Carbon‐13 and carbon‐14 labeled dabigatran etexilate and tritium labeled dabigatran

“…There is a risk of thromboembolism and bleeding as well despite careful individualized dose adjustment . A recent study found that the use of warfarin may be associated with an increased risk of serious hypoglycemic events among older people treated with sulfonylureas . Therefore, research efforts were focused on the identification of other direct thrombin inhibitors.…”