====== Glimepiride ======

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.

→ [[endocrine:sulfonylureas:start|Sulfonylureas]]

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===== Mechanism of Action =====

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

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===== Clinical Effects =====

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

Requires functional pancreatic beta cells.

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===== Pharmacokinetics =====

  * 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.

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===== Adverse Effects =====

Common:

  * Hypoglycemia
  * Weight gain

Higher risk in:

  * Elderly
  * Renal impairment
  * Irregular meal intake

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===== Contraindications / Cautions =====

Avoid in:

  * Type 1 Diabetes
  * History of severe hypoglycemia

Use caution in:

  * CKD
  * Elderly patients

Dose adjustments may be required.

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===== Glimepiride vs Other Sulfonylureas =====

Compared to:

  * [[endocrine:sulfonylureas:glyburide|Glyburide]] → lower hypoglycemia risk
  * [[endocrine:sulfonylureas:glipizide|Glipizide]] → longer duration of action

Glipizide is often preferred in elderly and CKD.

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===== Glimepiride vs Other Diabetes Agents =====

Compared to:

  * [[endocrine:biguanides:metformin|Metformin]] → more hypoglycemia, more weight gain
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]] → no weight loss, no ASCVD benefit
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]] → no heart failure benefit

Sulfonylureas are inexpensive but lack cardioprotective effects.

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===== Clinical Pearls =====

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

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===== Related =====

  * [[endocrine:sulfonylureas:start|Sulfonylureas]]
  * [[endocrine:sulfonylureas:glipizide|Glipizide]]
  * [[endocrine:sulfonylureas:glyburide|Glyburide]]
  * [[endocrine:biguanides:metformin|Metformin]]