Glimepiride is a second-generation sulfonylurea that stimulates pancreatic insulin secretion.

It is commonly used due to once-daily dosing and a lower risk of prolonged hypoglycemia compared to glyburide.

→ Sulfonylureas

Glimepiride binds to:

• Sulfonylurea receptor (SUR1)
• Component of the ATP-sensitive potassium (KATP) channel on pancreatic beta cells

Mechanism sequence:

• Closure of KATP channel
• Membrane depolarization
• Opening of voltage-gated calcium channels
• Increased intracellular calcium
• Insulin release

Important:

• Insulin secretion is NOT glucose-dependent
• Hypoglycemia risk remains significant

• Moderate HbA1c reduction
• Once-daily dosing
• Weight gain
• Lower hypoglycemia risk than glyburide, but still clinically relevant

Requires functional pancreatic beta cells.

• Once-daily dosing
• Hepatic metabolism
• Longer half-life than glipizide
• No strongly active metabolites like glyburide

Because of its duration, hypoglycemia can still occur — especially in elderly or CKD patients.

Common:

• Hypoglycemia
• Weight gain

Higher risk in:

• Elderly
• Renal impairment
• Irregular meal intake

Avoid in:

• Type 1 Diabetes
• History of severe hypoglycemia

Use caution in:

• CKD
• Elderly patients

Dose adjustments may be required.

Compared to:

• Glyburide → lower hypoglycemia risk
• Glipizide → longer duration of action

Glipizide is often preferred in elderly and CKD.

Compared to:

• Metformin → more hypoglycemia, more weight gain
• GLP-1 Receptor Agonists → no weight loss, no ASCVD benefit
• SGLT2 Inhibitors → no heart failure benefit

Sulfonylureas are inexpensive but lack cardioprotective effects.

• Second-generation sulfonylurea
• Once-daily dosing
• Hypoglycemia risk remains significant
• Causes weight gain
• Preferred over glyburide
• Requires functioning beta cells

• Sulfonylureas
• Glipizide
• Glyburide
• Metformin