What is the recommended dosage and management of Glypizide (Glipizide) for type 2 diabetes mellitus?

Glipizide Dosage and Management for Type 2 Diabetes Mellitus

The recommended initial dosage of glipizide for type 2 diabetes is 5 mg given approximately 30 minutes before breakfast, with conservative dosing of 2.5 mg for elderly patients or those with liver disease, and titration in increments of 2.5-5 mg based on blood glucose response. 1

Initial Dosing and Administration

• Glipizide should be administered approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia 1
• Standard initial dose is 5 mg once daily before breakfast 1
• For elderly patients, debilitated or malnourished patients, and those with impaired renal or hepatic function, start with a more conservative dose of 2.5 mg to avoid hypoglycemic reactions 1
• The extended-release formulation (GITS) provides more stable plasma drug concentrations and may optimize patient compliance with once-daily dosing 2

Dose Titration and Maintenance

• Dosage adjustments should be made in increments of 2.5 to 5 mg based on blood glucose response 1
• Allow at least several days between titration steps to assess response 1
• If response to a single dose is not satisfactory, dividing the dose may prove more effective 1
• Maximum recommended once-daily dose is 15 mg 1
• Doses above 15 mg should be divided and given before meals 1
• Maximum total daily dose is 40 mg 1
• Some patients may be effectively controlled on a once-daily regimen, while others show better response with divided dosing 1

Special Populations and Considerations

• For patients transitioning from insulin to glipizide: 1

  • If daily insulin requirement is ≤20 units, insulin may be discontinued and glipizide started at usual dosages
  • If daily insulin requirement is >20 units, reduce insulin dose by 50% and begin glipizide at usual dosages
  • Monitor urine for sugar and ketone bodies at least three times daily during insulin withdrawal

• For patients with renal impairment: 3

  • Use caution as renal impairment is associated with increased risk of severe hypoglycemia (odds ratio 4.0)
  • Patients with glipizide-associated hypoglycemia were found to have renal impairment more often than age- and sex-matched controls

• When transitioning from other oral hypoglycemic agents: 1

  • No transition period necessary when transferring patients to glipizide
  • When switching from longer half-life sulfonylureas (e.g., chlorpropamide), observe patients carefully for 1-2 weeks for hypoglycemia due to potential overlapping drug effects

Drug Interactions and Timing

• When coadministered with colesevelam, glipizide should be administered at least 4 hours prior to colesevelam to avoid reduced plasma concentration and total exposure 1
• Use caution with concomitant medications, particularly diuretics and benzodiazepines, as these were more commonly used by patients experiencing hypoglycemia 3

Monitoring and Safety

• Regular monitoring of blood glucose is essential to determine minimum effective dose, detect primary failure (inadequate response at maximum dose), and secondary failure (loss of adequate response after initial effectiveness) 1
• Glycosylated hemoglobin (HbA1c) levels are valuable for monitoring long-term response to therapy 1
• The incidence of hypoglycemic symptoms with glipizide extended-release is relatively low (≤3%) 2
• Severe hypoglycemia risk is higher in elderly patients (mean age 75 ± 9 years in reported cases) 3
• Hypoglycemia may be prolonged or recurrent for up to 60 hours in some patients 3

Combination Therapy

• When monotherapy is inadequate, glipizide can be effectively combined with metformin, showing greater HbA1c reduction than either agent alone 4
• The combination of glipizide and metformin addresses both impaired insulin secretion and insulin resistance 4
• Addition of glipizide to insulin therapy in patients with insulin-requiring type 2 diabetes can improve glucose control while reducing insulin dose requirements 5

Potential Pitfalls and Caveats

• Risk of hypoglycemia is increased in elderly patients, those with renal impairment, and patients taking multiple medications 3
• Patients with severe hypoglycemia may experience prolonged or recurrent episodes requiring extended monitoring 3
• Polypharmacy increases risk - patients experiencing hypoglycemia were found to be taking a median of 5 concomitant medications versus 2 in controls 3
• Regular blood glucose monitoring is critical during dose adjustments and when transitioning from other medications 1