What is the maximum recommended dose of glimepiride (sulfonylurea)?

Maximum Recommended Dose of Glimepiride

The maximum recommended dose of glimepiride is 8 mg once daily, administered with breakfast or the first main meal of the day. 1

Dosing Framework

Standard Maximum Dose

• The FDA-approved maximum daily dose is 8 mg once daily 1
• The American Diabetes Association confirms this 8 mg maximum in their 2025 guidelines 2
• Doses above 4 mg provide minimal additional glycemic benefit, as there is little difference in efficacy between 4 mg and 8 mg daily 3, 4

Dose Titration Approach

• Starting dose should be 1-2 mg once daily, with 1 mg preferred for patients at increased hypoglycemia risk 1
• After reaching 2 mg daily, increase in increments of 1-2 mg based on glycemic response 1
• Uptitration should occur no more frequently than every 1-2 weeks 1
• Most patients achieve adequate control with 1-4 mg daily, making doses above 4 mg rarely necessary 3, 4

Special Population Considerations

Renal Impairment

• Patients with eGFR 30-50 mL/min/1.73 m² should start at 1 mg daily with conservative titration due to hypoglycemia risk 5
• Glimepiride can be used cautiously in renal impairment, unlike glyburide which should be avoided when eGFR <50 mL/min/1.73 m² 5
• Pharmacokinetic studies show glimepiride clearance actually increases with declining renal function due to altered protein binding, making it safer than other sulfonylureas in this population 6

Elderly Patients

• Start at 1 mg daily in elderly patients who are at increased risk for hypoglycemia 1
• Use conservative titration schedules in this population 1

Critical Clinical Caveats

When Maximum Dose Is Insufficient

• If glycemic targets are not met at 15-20 mg daily (which exceeds the approved maximum), consider switching to insulin therapy rather than continuing dose escalation, as further increases rarely provide meaningful benefit and increase hypoglycemia risk 7
• The Endocrine Society recommends assessing kidney function before any dose increase, as eGFR <30 mL/min/1.73 m² warrants switching to alternative agents 7

Drug Interactions

• Glimepiride must be administered at least 4 hours prior to colesevelam, as colesevelam reduces glimepiride absorption and efficacy 1

Hypoglycemia Risk

• Hypoglycemia occurs in 10-20% of patients on monotherapy and ≥50% when combined with insulin 3
• Glimepiride has a lower hypoglycemia risk compared to glyburide, particularly in the first month of treatment 3