In an 86-year-old male diabetic patient on glyburide (Glibenclamide), metformin, and Farxiga (Dapagliflozin) with hypoglycemia, which medication should be adjusted first?

From the Guidelines

In an 86-year-old male diabetic patient experiencing hypoglycemia while on glyburide, metformin, and Farxiga, glyburide should be adjusted first. This recommendation is based on the most recent and highest quality study, which emphasizes the risks associated with sulfonylureas like glyburide in older adults 1. Glyburide is a longer-acting sulfonylurea that stimulates insulin secretion regardless of blood glucose levels, making it the most likely cause of hypoglycemia in this medication combination.

The dose of glyburide should be reduced or the medication discontinued entirely, depending on the severity and frequency of hypoglycemic episodes. Metformin and Farxiga have lower risks of causing hypoglycemia when used alone. Metformin works by decreasing hepatic glucose production and improving insulin sensitivity, while Farxiga is an SGLT2 inhibitor that promotes urinary glucose excretion.

Key points to consider when adjusting glyburide include:

• Age-related changes in drug metabolism and reduced hypoglycemia awareness in elderly patients like this 86-year-old 1
• The preference for sulfonylureas with a shorter duration of action, such as glipizide or glimepiride, over longer-acting ones like glyburide 1
• The importance of closely monitoring blood glucose after adjusting glyburide and educating the patient about hypoglycemia symptoms and management, including keeping fast-acting carbohydrates readily available.

Overall, the adjustment of glyburide is crucial in managing hypoglycemia in this patient, and it should be done with caution and close monitoring to prevent further episodes and ensure the best possible outcome in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

Table 5: Effects of Coadministered Drugs on Dapagliflozin Systemic Exposure ... Coadministered Drug (Dose Regimen)* Dapagliflozin (Dose Regimen)* Effect on Dapagliflozin Exposure [% Change (90% CI)] Cmax AUC† ... Glimepiride (4 mg) 20 mg ↔ ↔

Table 6: Effects of Dapagliflozin on the Systemic Exposures of Coadministered Drugs ... Coadministered Drug (Dose Regimen)* Dapagliflozin (Dose Regimen)* Effect on Coadministered Drug Exposure [% Change (90% CI)] Cmax AUC† ... Glimepiride (4 mg) 20 mg ↔ ↑13%[0%, ↑29%]

The patient is experiencing hypoglycemia with blood sugars in the 65-70 range. Given the medications the patient is on, Glyburide (Glibenclamide) is the most likely cause of hypoglycemia as it is a sulfonylurea that increases insulin secretion.

• The FDA drug label for Dapagliflozin does not provide guidance on managing hypoglycemia when used in combination with other diabetes medications.
• However, based on the mechanism of action of the medications, it is reasonable to consider adjusting the Glyburide dose first, as it has a higher risk of causing hypoglycemia compared to Metformin and Dapagliflozin.
• Metformin and Dapagliflozin are less likely to cause hypoglycemia, so adjusting these medications first may not be necessary.
• It is essential to monitor the patient's blood sugar levels closely and adjust the medications as needed to prevent further hypoglycemic episodes 2.

From the Research

Medication Adjustment for Hypoglycemia

The patient is experiencing hypoglycemia with blood sugar levels in the 65-70 range while taking glyburide, metformin, and Farxiga. To address this issue, it's essential to consider the medications that may be contributing to the hypoglycemia.

• Glyburide (Glibenclamide): Studies have shown that glyburide is associated with a higher risk of hypoglycemia compared to other sulfonylureas, such as glimepiride 3, 4. In fact, a study found that glyburide was associated with a higher incidence of severe hypoglycemia than glimepiride, with an incidence of 5.6/1000 person-years for glyburide and 0.86/1000 person-years for glimepiride 4.
• Metformin: Metformin is not typically associated with hypoglycemia, as it works by decreasing glucose production in the liver and increasing insulin sensitivity.
• Farxiga (Dapagliflozin): Farxiga is an SGLT2 inhibitor that works by increasing glucose excretion in the urine. While it can cause hypoglycemia, the risk is generally lower compared to sulfonylureas like glyburide.

Recommended Course of Action

Based on the evidence, it's recommended to adjust the glyburide dosage first, as it's the most likely contributor to the patient's hypoglycemia. Reducing the glyburide dosage or switching to a different sulfonylurea like glimepiride may help minimize the risk of hypoglycemia 5, 3, 4. Additionally, considering alternative medications like GLP-1 receptor agonists or SGLT2 inhibitors, which have a lower risk of hypoglycemia, may be beneficial for vulnerable patients like the 86-year-old male diabetic patient in question 6.

Key Considerations

• Monitor the patient's blood sugar levels closely after adjusting the glyburide dosage.
• Educate the patient on the signs and symptoms of hypoglycemia and how to manage it.
• Consider using continuous glucose monitoring (CGM) to help identify patterns of hypoglycemia and adjust the treatment plan accordingly 6.