What to do for a patient with diabetes on warfarin who refuses metformin and wants to take glipizide (a sulfonylurea) instead?

From the Guidelines

For a patient with diabetes on warfarin who refuses metformin and wants to take glipizide instead, this can be accommodated with careful monitoring, as glipizide may have a lower risk of hypoglycemia compared to other sulfonylureas 1.

Key Considerations

• Start glipizide at a low dose, typically 2.5-5 mg once daily before breakfast, and titrate gradually based on blood glucose response, up to a maximum of 40 mg daily (often given in divided doses).
• When initiating glipizide in a patient on warfarin, increase the frequency of INR monitoring initially (weekly for 2-3 weeks), as sulfonylureas may potentiate warfarin's effect through displacement from protein binding sites and through inhibition of warfarin metabolism.
• Watch for signs of hypoglycemia, which is a greater risk with sulfonylureas compared to metformin, especially in older adults or those with renal impairment, as noted in the management of hyperglycemia in type 2 diabetes 1.
• Also monitor for potential weight gain, as this is a common side effect of sulfonylureas.
• Educate the patient about recognizing and managing hypoglycemia, and consider recommending more frequent blood glucose self-monitoring during the initial adjustment period.

Rationale

While metformin is generally preferred as first-line therapy due to its cardiovascular benefits and lower hypoglycemia risk, as recommended by the American College of Physicians 1, glipizide can be an effective alternative when metformin cannot be used or is refused, with careful consideration of the potential risks and benefits, including the risk of adverse cardiovascular outcomes, which have been a concern with sulfonylureas in some observational studies, although recent systematic reviews have found no increase in all-cause mortality compared with other active treatments 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION There is no fixed dosage regimen for the management of diabetes mellitus with glipizide or any other hypoglycemic agent. In general, glipizide tablets should be given approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia. Initial Dose:The recommended starting dose is 5 mg, given before breakfast. Geriatric patients or those with liver disease may be started on 2.5 mg. Titration:Dosage adjustments should ordinarily be in increments of 2. 5–5 mg, as determined by blood glucose response. At least several days should elapse between titration steps. If response to a single dose is not satisfactory, dividing that dose may prove effective. The maximum recommended once daily dose is 15 mg. Doses above 15 mg should ordinarily be divided and given before meals of adequate caloric content. The maximum recommended total daily dose is 40 mg Maintenance:Some patients may be effectively controlled on a once-a-day regimen, while others show better response with divided dosing. Total daily doses above 15 mg should ordinarily be divided. Total daily doses above 30 mg have been safely given on a b.i. d. basis to long-term patients. In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions

For a patient with diabetes on warfarin who refuses metformin and wants to take glipizide,

• Monitor the patient's blood glucose levels and adjust the glipizide dose accordingly.
• Start with a low dose of 5 mg before breakfast and titrate as needed, with at least several days between titration steps.
• Be cautious of hypoglycemic reactions, especially in elderly patients or those with liver disease, and adjust the dose conservatively.
• Consider the potential interaction between glipizide and warfarin, and monitor the patient's INR levels closely 2.

From the Research

Patient Refusing Metformin and Wanting to Take Glipizide

• The patient is on warfarin and has diabetes, and is refusing to take metformin, instead wanting to take glipizide, a sulfonylurea 3.
• There is a risk of symptomatic hypoglycemia with therapeutic doses of metformin, although it is considered to have a low risk of inducing hypoglycemia compared to other oral hypoglycemics or insulin 4.
• The use of warfarin with sulfonylureas, such as glipizide, may increase the risk of serious hypoglycemia, with a rate ratio of 1.72 (95% CI, 1.29-2.29) for glipizide 3.
• Glipizide/metformin combination tablets have been shown to be effective in controlling HbA1c levels and reducing fasting plasma glucose levels, with a low incidence of hypoglycemia (12.6%) 5.
• Metformin is considered a first-line agent for the treatment of type 2 diabetes, particularly in obese and/or hyperlipidemic patients, and has a potentially beneficial effect on reducing serum lipid levels 6.
• The combination of glipizide and metformin may have an additive effect on glucose lowering, and patients should be counseled on the risk of hypoglycemia when taking these medications together 7.

Considerations for Patient Care

• The patient's refusal to take metformin and desire to take glipizide instead should be carefully considered, taking into account the potential risks and benefits of each medication.
• The patient's warfarin therapy should be closely monitored, as the use of sulfonylureas such as glipizide may increase the risk of serious hypoglycemia 3.
• The patient should be educated on the risks of hypoglycemia and the importance of monitoring their blood glucose levels regularly.
• Alternative treatment options, such as glipizide/metformin combination tablets, may be considered to help achieve better glycemic control with a lower risk of hypoglycemia 5.