Metformin (Biguanides)

Summary

Metformin is a member of the biguanide class of drugs that is commonly used for the treatment of type 2 diabetes mellitus. It works by inhibiting mGPD, which causes many downstream effects, including increased glycolysis and decreased hepatic gluconeogenesis. Metformin also decreases glucagon activity. The drug increases glucose uptake by cells, due to an increase in insulin sensitivity. 

The most important side effect of taking metformin is lactic acidosis. The risk of developing side effects like lactic acidosis is increased in people with decreased kidney function, so metformin should be used with caution in renal insufficiency. Patients starting metformin may experience nausea and vomiting that improves over time. If the drug is taken over a long period of time, Vitamin B12 Deficiency may develop. Metformin is notable for causing weight loss, and typically does not cause hypoglycemia in patients.

Key Points

• Biguanides
  • Drug Names
    • Metformin
  • Mechanism
    • Inhibits mGPD (mitochondrial glycerophosphate dehydrogenase)
      • Decreases hepatic gluconeogenesis
      • Decreases glucagon activity
      • Increases glycolysis
        • Appears to inhibit complex I of downstream electron transport chain, suppressing ATP formation
        • This can reduce ATP in the cell and stimulate more glycolysis as a compensatory response
      • Increases insulin sensitivity (peripheral glucose uptake)
  • Clinical Use
    • Treats diabetes mellitus
      • First-line therapy in type 2 diabetes mellitus
  • Side Effects
    • GI upset (nausea/vomiting)
    • Lactic acidosis
      • Use with Caution in renal insufficiency
    • Vitamin B12 (cobalamin) deficiency
      • Occurs in patients taking metformin over long periods of time
    • Weight loss
      • Often desired
    • Does not cause hypoglycemia
      • Does not cause insulin release directly but rather causes increase in sensitivity to insulin