metformin

Metformin is the usual first pill prescribed for type 2 diabetes, and its main trick is to tell the liver to stop overproducing sugar. In type 2 diabetes the liver keeps dumping glucose into the blood even when it is not needed; metformin turns that tap down. It does this without forcing the pancreas to release insulin, so on its own it almost never causes dangerously low blood sugar.

Mechanistically, metformin is a biguanide that suppresses hepatic gluconeogenesis, the liver's manufacture of new glucose, partly by acting on mitochondrial energy metabolism and activating the cellular energy sensor AMP-activated protein kinase. It also modestly improves insulin sensitivity in muscle and reduces glucose absorption from the gut. Importantly it is not metabolized; it is cleared unchanged by the kidneys, which is why kidney function governs its dosing.

Beyond lowering glucose, metformin tends to be weight-neutral or mildly weight-reducing and is inexpensive, which keeps it first-line worldwide. Its common nuisance is gastrointestinal upset, including nausea and diarrhoea, often eased by slow dose escalation or extended-release forms. Its rare but serious risk is lactic acidosis, a buildup of acid in the blood, which is why it is avoided or paused in severe kidney impairment, acute illness, or before procedures using iodinated contrast.