Introduction
Glimepiride is a second-generation sulfonylurea oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. As an insulin secretagogue, it belongs to a class of medications that stimulate pancreatic beta cells to release insulin. Approved by the FDA in 1995, glimepiride offers once-daily dosing and is often used as monotherapy or in combination with other antidiabetic agents when diet and exercise alone provide inadequate glycemic control.
Mechanism of Action
Glimepiride exerts its glucose-lowering effects primarily by stimulating insulin secretion from pancreatic beta cells. The drug binds to ATP-sensitive potassium channels on beta cell membranes, causing channel closure and subsequent membrane depolarization. This depolarization opens voltage-dependent calcium channels, leading to calcium influx and triggering insulin exocytosis. Additionally, glimepiride may exert extrapancreatic effects including increased insulin sensitivity in peripheral tissues and reduced hepatic glucose production.
Indications
- Management of type 2 diabetes mellitus as an adjunct to diet and exercise
- Monotherapy when glycemic control cannot be achieved by nonpharmacological methods alone
- Combination therapy with other oral antidiabetic agents or insulin when additional glycemic control is needed
Dosage and Administration
Initial dose: 1-2 mg once daily with breakfast or first main meal Maintenance dose: 1-4 mg once daily (maximum recommended dose: 8 mg daily) Dose titration: Increase by 1-2 mg at 1-2 week intervals based on glycemic response Special populations:- Renal impairment: Use caution; initial dose 1 mg daily with careful titration
- Hepatic impairment: Use caution; may reduce glucose counterregulation
- Elderly: Start with 1 mg daily; increased risk of hypoglycemia
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Completely absorbed from GI tract; bioavailability approximately 100% Distribution: Protein binding >99%; volume of distribution 8.8 L Metabolism: Extensive hepatic metabolism via CYP2C9 to inactive metabolites Elimination: Half-life 5-8 hours; excreted primarily in urine (60%) and feces (40%) Onset of action: Within 1 hour; peak effect at 2-3 hours Duration: 24 hours (allowing once-daily dosing)Contraindications
- Hypersensitivity to glimepiride or other sulfonylureas/sulfonamides
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal or hepatic impairment
- Concomitant use with bosentan
Warnings and Precautions
Hypoglycemia: Risk increased with renal/hepatic impairment, elderly, debilitated, or malnourished patients Cardiovascular mortality: Increased cardiovascular mortality reported with other sulfonylureas Hemolytic anemia: Possible in patients with glucose-6-phosphate dehydrogenase deficiency Syndrome of inappropriate antidiuretic hormone (SIADH): Water retention and hyponatremia reported Hepatic porphyria: May exacerbate acute porphyric attacks Stress situations: May require temporary discontinuation during major surgery, trauma, or infectionDrug Interactions
Strong CYP2C9 inhibitors: Fluconazole, amiodarone - may increase glimepiride levels Strong CYP2C9 inducers: Rifampin - may decrease glimepiride levels Other hypoglycemic agents: Insulin, metformin, thiazolidinediones - additive hypoglycemic effects Beta-blockers: May mask hypoglycemic symptoms and impair glucose recovery Alcohol: May cause disulfiram-like reaction and potentiate hypoglycemia Warfarin: Possible potentiation of anticoagulant effect NSAIDs, salicylates: May enhance hypoglycemic effectAdverse Effects
Common (≥1%):- Hypoglycemia (0.9-1.7%)
- Headache (1.1%)
- Nausea (1.1%)
- Dizziness (0.9%)
- Allergic skin reactions (urticaria, pruritus)
- Gastrointestinal disturbances
- Visual disturbances
- Hematologic effects (leukopenia, thrombocytopenia)
- Hyponatremia
- Elevated liver enzymes
- Severe hypoglycemia
- Hemolytic anemia
- Hepatitis
- Stevens-Johnson syndrome
- Syndrome of inappropriate antidiuretic hormone (SIADH)
Monitoring Parameters
- Fasting blood glucose and HbA1c (every 3 months until stable)
- Regular self-monitoring of blood glucose
- Renal function (serum creatinine) at baseline and periodically
- Liver function tests at baseline and periodically
- Complete blood count periodically
- Signs and symptoms of hypoglycemia
- Weight changes
- Serum sodium levels (if symptoms suggest SIADH)
Patient Education
- Take medication with breakfast or first main meal of the day
- Understand signs and symptoms of hypoglycemia (sweating, tremor, palpitations)
- Always carry a fast-acting glucose source
- Regular blood glucose monitoring is essential
- Do not skip meals while taking glimepiride
- Avoid excessive alcohol consumption
- Inform all healthcare providers about glimepiride use
- Report any unusual symptoms, skin reactions, or dark urine
- Understand that glimepiride controls but does not cure diabetes
- Maintain regular exercise and dietary regimen as prescribed
References
1. American Diabetes Association. (2023). Standards of Medical Care in Diabetes. Diabetes Care, 46(Supplement 1), S1-S291. 2. Glimepiride prescribing information. (2022). U.S. Food and Drug Administration. 3. Del Prato, S., & Pulizzi, N. (2006). The place of sulfonylureas in the therapy for type 2 diabetes mellitus. Metabolism, 55(5 Suppl 1), S20-S27. 4. Haas, B., Eckstein, N., & Pfeifer, V. (2019). Efficacy and safety of glimepiride in the management of type 2 diabetes: Evidence from clinical trials and real-world studies. Diabetes Research and Clinical Practice, 157, 107843. 5. Holstein, A., & Beil, W. (2009). Oral antidiabetic drug metabolism: Pharmacogenomics and drug interactions. Expert Opinion on Drug Metabolism & Toxicology, 5(2), 225-241. 6. UK Prospective Diabetes Study (UKPDS) Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet, 352(9131), 837-853.