What causes recurrent hypoglycemia in patients taking glipizide (a sulfonylurea)

From the Guidelines

Glipizide should be discontinued in patients experiencing recurrent hypoglycemia and replaced with an alternative diabetes medication, as recommended by the most recent guidelines 1. Hypoglycemia is a common side effect of sulfonylureas like glipizide, which work by stimulating insulin release from pancreatic beta cells regardless of blood glucose levels. Consider switching to medications with lower hypoglycemia risk such as metformin (starting at 500mg daily, increasing to 1000mg twice daily as tolerated), DPP-4 inhibitors like sitagliptin (100mg daily), or GLP-1 receptor agonists. Before changing medication, evaluate contributing factors including irregular meal timing, excessive alcohol consumption, renal impairment, or drug interactions, as suggested by previous studies 1. Patients should be educated to recognize hypoglycemia symptoms (shakiness, confusion, sweating) and instructed to carry fast-acting carbohydrates like glucose tablets. Blood glucose monitoring frequency should be increased during medication transitions, and patients should temporarily reduce glipizide dosage while awaiting their follow-up appointment. Elderly patients and those with renal impairment are particularly susceptible to hypoglycemia with sulfonylureas and may benefit from medications with better safety profiles, as noted in the 2018 ACC expert consensus decision pathway 1.

Some key points to consider when managing patients on glipizide include:

• Monitoring for signs of hypoglycemia, such as shakiness, confusion, and sweating
• Educating patients on the importance of carrying fast-acting carbohydrates like glucose tablets
• Adjusting medication dosages as needed to minimize the risk of hypoglycemia
• Considering alternative medications with lower hypoglycemia risk for patients experiencing recurrent hypoglycemia
• Individualizing treatment plans to each patient's specific needs and medical history, as recommended by the American College of Cardiology task force on expert consensus decision pathways 1.

It is essential to prioritize the patient's safety and well-being when managing diabetes medications, particularly those with a high risk of hypoglycemia like glipizide, as emphasized in the 2009 scientific statement from the American Heart Association 1. By taking a proactive and patient-centered approach to managing diabetes medications, healthcare providers can help minimize the risk of hypoglycemia and improve overall patient outcomes, as suggested by the 2018 ACC expert consensus decision pathway 1.

From the FDA Drug Label

Renal or hepatic insufficiency may cause elevated blood levels of glipizide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used

• Causes of recurrent hypoglycemia in patients taking glipizide include:
  • Renal or hepatic insufficiency
  • Deficient caloric intake
  • Severe or prolonged exercise
  • Alcohol ingestion
  • Use of more than one glucose-lowering drug Recurrent hypoglycemia in patients taking glipizide may be caused by these factors, as they can increase the risk of hypoglycemic reactions 2

From the Research

Causes of Recurrent Hypoglycemia in Patients Taking Glipizide

• Renal impairment is a significant factor, as patients with glipizide-associated hypoglycemia were found to have renal impairment more often than age- and sex-matched controls treated with glipizide 3
• The use of concomitant drugs, such as diuretics and benzodiazepines, is also a contributing factor, as hypoglycemic patients were found to be using more concomitant drugs than controls 3
• The risk of hypoglycemia is higher with glipizide compared to other medications, such as saxagliptin and sitagliptin, when added to metformin therapy 4, 5
• Patient characteristics, such as age and glycemic efficacy, may also influence the risk of hypoglycemic events 5
• The dose of glipizide may also play a role, as higher doses are associated with an increased risk of hypoglycemia 6

Comparison with Other Medications

• Glipizide is associated with a higher risk of serious hypoglycemia compared to metformin, with an adjusted hazard ratio of 2.57 (2.38-2.78) 6
• Sulfonylureas, including glipizide, are associated with the highest rates of serious hypoglycemia compared to other oral antidiabetic monotherapies 6
• DPP-4 inhibitors, such as saxagliptin and linagliptin, may be considered a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin, due to their lower risk of hypoglycemia 7