Maximum Doses of Sulfonylureas
The maximum recommended daily doses are: Glimepiride 8 mg, Gliclazide 320 mg (immediate-release), Glipizide 40 mg, and Glibenclamide should be avoided in renal impairment (eGFR <50 mL/min/1.73 m²) due to high hypoglycemia risk. 1, 2, 3, 4
Glimepiride
- Maximum dose: 8 mg once daily, administered with breakfast or the first main meal 1, 5
- Start at 1-2 mg daily, with uptitration in 1-2 mg increments every 1-2 weeks based on glycemic response 1
- Doses above 4 mg rarely provide meaningful additional benefit, and further escalation increases hypoglycemia risk without substantial glycemic improvement 5, 6
- In renal impairment (eGFR 30-50 mL/min/1.73 m²), start at 1 mg daily with conservative titration 5
- If glycemic targets are not met at 8 mg daily, switch to insulin therapy rather than continuing dose escalation 5
Gliclazide
- Maximum dose: 320 mg daily for immediate-release formulation 3
- Modified-release formulation maximum is 120 mg daily 3
- Can be used cautiously in renal impairment, with dose reduction needed when eGFR <30 mL/min/1.73 m² 4
- Primarily metabolized in the liver, making it safer than renally-excreted sulfonylureas in kidney disease 4
Glipizide
- Maximum dose: 40 mg daily 2
- Maximum once-daily dose is 15 mg; doses above 15 mg should be divided and given before meals 2
- Start at 5 mg before breakfast (2.5 mg in elderly or those with liver disease) 2
- Titrate in 2.5-5 mg increments with several days between adjustments 2
- In renal impairment (eGFR 30-50 mL/min/1.73 m²), start conservatively at 2.5 mg daily 7
- If glycemic targets are not met at 15-20 mg daily, switch to insulin rather than escalating to maximum dose 7
Glibenclamide (Glyburide)
- Avoid this agent entirely in patients with eGFR <50 mL/min/1.73 m² due to high risk of severe, prolonged hypoglycemia from renal excretion of active metabolites 4, 5
- This is the most dangerous sulfonylurea in renal impairment and should not be used when kidney function is reduced 4
Critical Clinical Caveats
- Assess kidney function (eGFR) before initiating any sulfonylurea and before each dose increase 5, 7
- When eGFR <30 mL/min/1.73 m², consider switching to alternative agents entirely rather than continuing sulfonylureas 5, 7
- Hypoglycemia risk increases substantially at higher doses without proportional glycemic benefit, particularly in elderly patients and those with renal impairment 5, 1, 2
- Temporarily suspend sulfonylureas during acute illness, dehydration, or before procedures requiring bowel preparation 4
- Modern diabetes management prioritizes SGLT2 inhibitors and GLP-1 receptor agonists over sulfonylureas in patients with cardiovascular disease, heart failure, or chronic kidney disease due to superior cardiovascular and renal protection 7