====== Sulfonylureas ======

Sulfonylureas are insulin secretagogues that stimulate pancreatic beta cells to release insulin.

They lower blood glucose by increasing endogenous insulin secretion.

They carry a significant risk of hypoglycemia.

→ [[endocrine:diabetes:start|Diabetes Pharmacology]]

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

Sulfonylureas act on pancreatic beta cells.

They bind to:

  * The sulfonylurea receptor (SUR1)
  * Part of the ATP-sensitive potassium (KATP) channel

Mechanism sequence:

  * KATP channel closure
  * Membrane depolarization
  * Opening of voltage-gated calcium channels
  * Increased intracellular calcium
  * Insulin exocytosis

Important:

  * Insulin release is NOT glucose-dependent.
  * Hypoglycemia can occur even at low glucose levels.

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===== Generations =====

First Generation:

  * Chlorpropamide
  * Tolbutamide

Second Generation (more commonly used):

  * [[endocrine:sulfonylureas:glipizide|Glipizide]]
  * [[endocrine:sulfonylureas:glyburide|Glyburide]]
  * [[endocrine:sulfonylureas:glimepiride|Glimepiride]]

Second-generation agents are more potent and have fewer side effects.

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

  * Moderate HbA1c reduction
  * Rapid onset
  * Weight gain
  * High hypoglycemia risk

They require functioning pancreatic beta cells.

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

Common:

  * Hypoglycemia
  * Weight gain

Serious:

  * Severe hypoglycemia (especially in elderly)
  * Rare hyponatremia (chlorpropamide)
  * Rare hematologic reactions

Risk factors for hypoglycemia:

  * Elderly patients
  * Renal impairment
  * Irregular meals
  * Alcohol use

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===== Contraindications =====

  * Type 1 Diabetes
  * History of severe hypoglycemia
  * Advanced renal failure (dose caution)

Use caution in:

  * Elderly patients
  * CKD

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===== Sulfonylureas vs Other Diabetes Agents =====

Compared to:

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

Sulfonylureas are inexpensive but lack cardioprotective benefit.

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

  * Close KATP channels in beta cells
  * Insulin release is NOT glucose-dependent
  * High hypoglycemia risk
  * Cause weight gain
  * Require functional beta cells
  * Often avoided in elderly when safer options available

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===== Related =====

  * [[endocrine:diabetes:start|Diabetes Pharmacology]]
  * [[endocrine:biguanides:metformin|Metformin]]
  * [[endocrine:tzds:start|Thiazolidinediones]]
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]