Maximum Dose of Glipizide
The maximum recommended total daily dose of glipizide is 40 mg, with doses above 15 mg daily ordinarily being divided and given before meals. 1
Dosing Guidelines
Initial Dosing
- Standard starting dose: 5 mg once daily, given approximately 30 minutes before breakfast
- For elderly patients or those with liver disease: 2.5 mg once daily
Titration
- Dose adjustments should be made in increments of 2.5-5 mg based on blood glucose response
- Allow several days between titration steps
- If response to a single dose is not satisfactory, dividing that dose may prove effective
Maximum Dosing
- Maximum recommended once-daily dose: 15 mg
- Maximum recommended total daily dose: 40 mg
- Doses above 15 mg should be divided and given before meals
- Total daily doses above 30 mg have been safely given on a twice-daily basis to long-term patients 1
Special Considerations
Renal Impairment
- For patients with eGFR 30-50 mL/min/1.73 m²: No dose adjustment required, but conservative initial dosing (e.g., 2.5 mg daily) is recommended
- For patients with eGFR <30 mL/min/1.73 m²: Use with caution, especially with long-acting formulations due to risk of hypoglycemia 2
Extended-Release Formulation
- Glipizide GITS (Gastrointestinal Therapeutic System): Maximum effective dose is 20 mg daily for fasting plasma glucose control, with maximal HbA1c reduction achieved at 5 mg daily 3
- Maximum dose of extended-release (XL) formulation: 20 mg daily 2
Efficacy Considerations
Research has shown limited additional benefit when increasing glipizide doses beyond certain thresholds:
- A study comparing different glipizide doses found little to no additional benefit when increasing beyond 10 mg once daily, and higher doses may actually reduce beta-cell function 4
- Pharmacodynamic analysis indicates maximal efficacy is achieved at 20 mg for fasting plasma glucose and at 5 mg for HbA1c reduction 3
Safety Considerations
- Higher doses increase the risk of hypoglycemia, particularly in elderly patients, those with renal impairment, and patients taking multiple medications 5
- Severe hypoglycemia has been reported with glipizide, particularly in elderly patients with renal impairment 5
- When switching from longer-acting sulfonylureas to glipizide, patients should be observed carefully for 1-2 weeks due to potential overlapping drug effects 1
Clinical Pearls
- Doses above 15 mg should be divided to improve efficacy and reduce side effects
- Total daily doses above 30 mg should be carefully monitored for hypoglycemia
- For most patients, the optimal balance of efficacy and safety is achieved at doses below the maximum
- When colesevelam is coadministered with glipizide, glipizide should be administered at least 4 hours prior to colesevelam 1