Glimepiride. A review of its use in the management of type 2 diabetes mellitus.

Glimepiride is a sulphonylurea agent that stimulates insulin release from pancreatic beta-cells and may act via extrapancreatic mechanisms. It is administered once daily to patients with type 2 (non-insulin-dependent) diabetes mellitus in whom glycaemia is not controlled by diet and exercise alone, and may be combined with insulin in patients with secondary sulphonylurea failure. The greatest blood glucose lowering effects of glimepiride occur in the first 4 hours after the dose. Glimepiride has fewer and less severe effects on cardiovascular variables than glibenclamide (glyburide). Pharmacokinetics are mainly unaltered in elderly patients or those with renal or liver disease. Few drug interactions with glimepiride have been documented. In patients with type 2 diabetes, glimepiride has an effective dosage range of 0.5 to 8 mg/day, although there is little difference in efficacy between dosages of 4 and 8 mg/day. Glimepiride was similar in efficacy to glibenclamide and glipizide in 1-year studies. However, glimepiride appears to reduce blood glucose more rapidly than glipizide over the first few weeks of treatment. Glimepiride and gliclazide were compared in patients with good glycaemic control at baseline in a 14-week study that noted no differences between their effects. Glimepiride plus insulin was as effective as insulin plus placebo in helping patients with secondary sulphonylurea failure to reach a fasting blood glucose target level of < or = 7.8 mmol/L, although lower insulin dosages and more rapid effects on glycaemia were seen with glimepiride. Although glimepiride monotherapy was generally well tolerated, hypoglycaemia occurred in 10 to 20% of patients treated for < or = 1 year and > or = 50% of patients receiving concomitant insulin for 6 months. Pooled clinical trial data suggest that glimepiride may have a lower incidence of hypoglycaemia than glibenclamide, particularly in the first month of treatment. Dosage is usually started at 1 mg/day, titrated to glycaemic control at 1- to 2-week intervals to a usual dosage range of 1 to 4 mg/day (maximum 6 mg/day in the UK or 8 mg/day in the US). Glimepiride is a conveniently administered alternative to other sulphonylureas in patients with type 2 diabetes mellitus not well controlled by diet alone. Its possible tolerability advantages and use in combination with other oral antidiabetic drugs require further study. Glimepiride is also reported to reduce exogenous insulin requirements in patients with secondary sulphonylurea failure when administered in combination with insulin.