MOA

• Very complicated! TLDR Reduction in hepatic glucose production (gluconeogenesis) and increase in the peripheral utilisation of glucose.
• inhibits complex 1 of electron transport chain in mitochondria, increasing ADP:ATP and AMP:ATP → this activates AMP-activated protein kinase (AMPK)
• AMPK provides a very important role in a variety of metabolic processes including
  • Increasing the expression of nuclear receptors that inhibit expression of genes important for gluconeogenesis thus reduces hepatic glucose production (reduces gluconeogenesis), which is markedly increased in type 2 diabetes
  • increases translocation of GLUT-4 → increase glucose uptake and utilisation in skeletal muscle
  • reduces carbohydrate absorption, increase fatty acid oxidation
• Thus reduce blood glucose, increase insulin sensitivity and therefore reduce hyperinsulinemia associated with insulin resistance

Preserves the pancreas as well

indication

• Type 2 diabetics (first line)
• Can also be used in PCOS

Contraindication

• Metformin is contraindicated in patients with a creatine clearance of less than 60mL/min, moderate-severe heart failure, acute MI and those undergoing major surgery
• Reduces renal function
• • need to check if having a CT**

Route

Oral