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.

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:

• Type 2 Diabetes Mellitus

• Metformin (Glucophage®)

Historical (withdrawn):

• Phenformin (withdrawn due to lactic acidosis risk)

Metformin is the only biguanide currently used in clinical practice.

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.

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:

• GLP-1 Receptor Agonists
• SGLT2 Inhibitors
• Thiazolidinediones
• Insulin Therapy

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.

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.

• Metformin
• Diabetes Pharmacology
• Endocrine Pharmacology
• Cardiovascular Pharmacology