Recommended Starting Doses for Sulfonylureas
For glimepiride, start at 1 mg once daily with breakfast or the first main meal; for glipizide, start at 2.5-5 mg daily (or 2.5 mg in renal impairment); for glyburide, start at 1.25-2.5 mg daily with breakfast, using the lower dose in patients at increased risk of hypoglycemia. 1, 2, 3, 4
Glimepiride (Amaryl)
Standard Dosing
- Initial dose: 1 mg once daily with breakfast or the first main meal 3, 5, 6
- Titrate at 1-2 week intervals based on glycemic response 5, 7
- Usual maintenance range: 1-4 mg/day 5, 6
- Maximum dose: 8 mg/day (though 4-8 mg shows minimal efficacy difference) 5, 6
Renal Impairment Considerations
- eGFR >50 mL/min/1.73 m²: No dose adjustment required 2, 3
- eGFR 30-50 mL/min/1.73 m²: Start at 1 mg daily with conservative titration due to hypoglycemia risk 1, 3
- eGFR <30 mL/min/1.73 m²: Consider switching to alternative agents 3
Glipizide (Glucotrol)
Standard Dosing
- Initial dose: 2.5-5 mg daily with breakfast or the first main meal 4
- For patients at increased risk of hypoglycemia: Start at 2.5 mg daily 2
- Titrate in increments of no more than 2.5 mg at weekly intervals 4
- Usual maintenance range: 5-15 mg/day 1
- Maximum dose: 20 mg/day (doses >10 mg may require twice-daily dosing) 4
Renal Impairment Considerations
- eGFR >50 mL/min/1.73 m²: No dose adjustment required 1
- eGFR 30-50 mL/min/1.73 m²: Start conservatively at 2.5 mg daily 2
- Extended-release formulations carry higher hypoglycemia risk in renal impairment; prefer immediate-release 2
Glyburide/Glibenclamide (DiaBeta)
Standard Dosing
- Initial dose: 2.5-5 mg daily with breakfast or the first main meal 4
- For patients more sensitive to hypoglycemic drugs: Start at 1.25 mg daily 4
- Titrate in increments of no more than 2.5 mg at weekly intervals 4
- Usual maintenance range: 1.25-20 mg/day 4
- Maximum dose: 20 mg/day 4
Critical Renal Impairment Warning
- Avoid glyburide if eGFR <50 mL/min/1.73 m² due to high risk of prolonged hypoglycemia 1, 2
- Glyburide is generally not recommended in chronic kidney disease 1
Important Clinical Caveats
Hypoglycemia Risk Management
- Sulfonylureas carry inherent hypoglycemia risk, particularly in elderly patients, those with renal impairment, and when combined with insulin 1, 4
- Glimepiride may have lower hypoglycemia incidence compared to glyburide, especially in the first month of treatment 5, 6
- Patients should be educated on recognizing and managing hypoglycemic episodes 8
Modern Treatment Context
- Sulfonylureas are not preferred first-line agents in patients with established cardiovascular disease, heart failure, or chronic kidney disease—SGLT2 inhibitors and GLP-1 receptor agonists with proven cardiovascular and renal benefits should be prioritized 2
- Avoid chlorpropamide (first-generation sulfonylurea) during Ramadan fasting due to high risk of prolonged, unpredictable hypoglycemia 1
Dose Escalation Limits
- If glycemic targets are not met at maximum approved doses (glimepiride 8 mg, glipizide 20 mg, glyburide 20 mg), consider switching to insulin therapy rather than continuing dose escalation, as further increases rarely provide meaningful benefit and increase hypoglycemia risk 2, 3
- Assess kidney function before any dose increase, as declining eGFR fundamentally changes the dosing approach 2