What is Glibenclamide?

Glibenclamide: A Sulfonylurea Medication for Type 2 Diabetes

Glibenclamide (also known as glyburide in the US and Canada) is a second-generation sulfonylurea medication primarily used for treating type 2 diabetes that lowers blood glucose by enhancing insulin secretion from pancreatic beta cells, but carries a substantially higher risk of hypoglycemia compared to other sulfonylureas, making it a less preferable choice, especially in elderly patients. 1, 2

Mechanism of Action

Glibenclamide works through the following mechanisms:

• Binds to and blocks ATP-dependent potassium (KATP) channels in pancreatic beta cells, leading to cell membrane depolarization, calcium influx, and insulin release 3
• Inhibits beta-cell carnitine palmitoyltransferase 1 (CPT-1) activity, suppressing fatty acid oxidation and enhancing diacylglycerol formation and PKC activation, which contributes to insulin exocytosis 4
• Can reduce HbA1c levels by 1.0% to 1.5% 1

Clinical Efficacy

• Effective in lowering blood glucose levels in type 2 diabetes patients
• Can be used as monotherapy or in combination with other antidiabetic medications, particularly metformin 5
• Has been shown to improve fasting plasma glucose, HbA1c, and postprandial glucose control 5

Important Side Effects and Risks

• Hypoglycemia: Carries a significantly higher risk of hypoglycemia compared to other second-generation sulfonylureas (gliclazide, glimepiride, glipizide) 1, 2

  • Can cause prolonged and life-threatening hypoglycemic episodes, particularly in elderly patients 6
  • Fatal outcomes have been reported even with small doses (2.5-5 mg/day) 6

• Weight gain: Typically around 2 kg following initiation of therapy 1, 2

• Other adverse effects:

  • Hyperlipidemia (25-50% of patients) with increased serum triglycerides 2
  • Elevation in liver transaminases (13-16% of patients) 2
  • Rare cases of toxic hepatitis 2

Risk Factors for Severe Hypoglycemia

• Advanced age (median age of patients with hypoglycemia is 75 years) 6
• Previous strokes and cardiac disorders 6
• Impaired renal function 6
• Low food intake or diarrhea 6
• Alcohol consumption 6
• Drug interactions 6

Special Populations and Contraindications

• Elderly patients: Higher risk of hypoglycemia; alternative sulfonylureas are preferable 2, 6
• Renal impairment: Should be used with caution; other sulfonylureas may be safer options 2
• Severe hepatic impairment: Contraindicated 2
• Pregnancy: Contraindicated due to risk of neonatal hypoglycemia 2

Therapeutic Considerations

• Starting dose should be low with gradual titration to minimize adverse effects 5
• Regular blood glucose monitoring is essential, especially when initiating therapy 2
• Periodic liver function tests and lipid profile monitoring are recommended 2
• In patients with type 2 diabetes uncontrolled on monotherapy, combination with metformin may be beneficial 5
• For patients at risk of cardiovascular disease, alternative medications should be considered 5

Alternative Medications

• Other second-generation sulfonylureas (gliclazide, glimepiride, glipizide) have lower hypoglycemia risk 1
• Metformin remains the first-line therapy for most patients with type 2 diabetes 1
• DPP-4 inhibitors in combination with metformin may offer a safer alternative to glibenclamide-metformin combinations for some patients 5

In clinical practice, the high risk of hypoglycemia associated with glibenclamide, particularly in elderly patients and those with renal impairment, should prompt careful consideration of alternative medications with more favorable safety profiles.