INTRODUCTION
Metformin is an oral hypoglycemia drug belonging to the biguanide class. It widely used as first-line therapeutic drug in type 2 diabetes mellitus. Metformin is not metabolised in the body and excreted as unchanged form through the kidneys.
Why not metabolized ?
1.Chemical nature of metformin
Metformin is a small, highly polar and hydrophilic drug molecule in nature so, it does not easily cross cell membranes and does not enter hepatic enzyme systems which responsible for drug metabolism.
2. No need for metabolic conversion
Drugs are usually metabolised to make them more water-soluble for excretion. Since metformin is already water-soluble, the body does not need to modify it chemically.
3. Renal excretion without metabolism
Metformin is eliminated unchanged in urine by glomerular filtration,it Active tubular secretion nearly 90–100% of the administered dose is excreted without any metabolic transformation
4. Lack of interaction with liver enzymes
Most drugs are metabolised in the liver by cytochrome P450 (CYP450) enzymes. Metformin does not bind to it or it does not activate these enzymes, so it does not undergo Phase I or Phase II metabolic reactions.
CONCLUSION
Metformin is excreted unchanged by the kidneys, making renal function a critical factor in its safe use. This unique property explains why metformin is safe in liver disease but contraindicated in renal impairment, where accumulation may lead to lactic acidosis.Metformin is not metabolised because of its high polarity, hydrophilic nature, and lack of affinity for hepatic CYP450 enzymes.
If metformin is not metabolised, why is kidney function so important during its use?
MBH/PS