====== Biguanides ======

Biguanides are oral antihyperglycemic agents that reduce plasma glucose primarily by suppressing hepatic gluconeogenesis.

They improve insulin sensitivity without stimulating insulin secretion and therefore carry minimal hypoglycemia risk.

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===== Class Overview =====

Biguanides lower blood glucose by:

  * Decreasing hepatic glucose production
  * Improving peripheral insulin sensitivity
  * Enhancing glucose uptake in skeletal muscle

They do NOT increase insulin secretion.

Primary clinical use:
  * [[endocrine:diabetes:start|Type 2 Diabetes Mellitus]]

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===== Agents in This Class =====

  * [[endocrine:biguanides:metformin|Metformin]] (Glucophage®)

Historical (withdrawn):
  * Phenformin (withdrawn due to lactic acidosis risk)

Metformin is the only biguanide currently used in clinical practice.

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===== Mechanism of Action (Class Effect) =====

Primary intracellular action:

  * Inhibition of mitochondrial respiratory chain complex I
  * ↑ AMP:ATP ratio
  * Activation of AMP-activated protein kinase (AMPK)

Physiologic outcomes:

  * ↓ Hepatic gluconeogenesis
  * ↓ Fasting plasma glucose
  * ↑ Peripheral glucose uptake
  * Improved insulin sensitivity

Does NOT stimulate pancreatic beta cells.

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===== Clinical Role in Therapy =====

Biguanides are:

  * First-line therapy for most patients with Type 2 DM
  * Weight-neutral or modestly weight-reducing
  * Associated with cardiovascular benefit (UKPDS data)

Often combined with:

  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]
  * [[endocrine:tzds:start|Thiazolidinediones]]
  * [[endocrine:insulin:start|Insulin Therapy]]

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===== Safety Profile =====

Hypoglycemia:
  * Rare as monotherapy

Major Risk:
  * Lactic acidosis (rare but serious)

Risk factors:

  * Advanced renal impairment
  * Severe hepatic disease
  * Hypoxic states

Renal monitoring is essential.

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===== Why This Class Matters =====

Biguanides target the core pathophysiology of Type 2 DM:

  * Hepatic overproduction of glucose

Unlike secretagogues, they do not exhaust beta cells.

They remain foundational in cardiometabolic disease management.

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===== Related =====

  * [[endocrine:biguanides:metformin|Metformin]]
  * [[endocrine:diabetes:start|Diabetes Pharmacology]]
  * [[endocrine:start|Endocrine Pharmacology]]
  * [[cardio:intro:start|Cardiovascular Pharmacology]]