Metformin

Metformin is one of the oldest antidiabetic medicines available. It works by blocking the liver’s ability to produce glucose from fats and increases sensitivity to the insulin that the pancreas is producing. It is only effective if there are some residual functioning pancreatic islet cells. Metformin is the drug of choice in overweight individuals. Gastrointestinal side effects are initially common but dose titration often helps. 

Sulfonylureas

Sulfonylureas work by increasing insulin production and improving its use by the body but, again, only when some residual pancreatic beta-cell activity is present. Sulfonylureas are considered for those who are not overweight, as they encourage weight gain, or in whom metformin is contraindicated or not tolerated. Gliclazide, glimepiride, glipizide and tolbutamide are all examples of sulfonylureas.

Glibenclamide is a longer acting sulfonylurea that should be avoided in the elderly due to the risk of falls from hypoglycaemia. 

Pioglitazone

Pioglitazone reduces peripheral insulin resistance, which leads to a reduction in blood glucose concentration. Care must be taken because it can cause fluid retention, which can exacerbate or precipitate heart failure. Fluid retention can also cause weight gain in addition to the accumulation of fat associated with this drug.