Anti-diabetic drugs

Oral hypoglycaemic agents

Sulphonlyureas

Sulfonylureas, such as gliclazide, glimepiride, glipizide, and tolbutamide, primarily work by augmenting insulin secretion from pancreatic β-cells. They do this by blocking ATP-sensitive potassium (KATP) channels on β-cell membranes, leading to cell depolarisation, calcium influx, and subsequent insulin release. They do not stimulate insulin production but enhance the release of preformed insulin from existing β-cells.

Since their action depends on functional pancreatic β-cells, sulfonylureas are only effective in patients with residual β-cell activity (e.g., type 2 diabetes but not type 1 diabetes, where β-cell destruction has occurred). As a result they may cause hypoglycaemia. Hypoglycaemia is more likely with long-acting sulfonylureas such as glimepiride, which have been associated with severe, prolonged and sometimes fatal cases of hypoglycaemia. Sulfonylureas are also associated with modest weight gain, probably due to increased plasma-insulin concentrations.

Anti-hyperglycaemic agents

Biguanides

The most commonly used biguanide in the UK is metformin. Metformin decreases blood glucose levels via decreasing hepatic glucose production (gluconeogenesis), decreasing intestinal absorption of glucose, and increasing insulin sensitivity by increasing peripheral glucose uptake and utilisation.

It is not associated with weight gain, and does not stimulate insulin secretion and therefore, when given alone, does not cause hypoglycaemia. Gastrointestinal upset is a common side effect. Lactic acidosis is a rare side effect.