GLIMEPIRIDE - A REVIEW OF ITS USE IN THE MANAGEMENT OF TYPE-2 DIABETES-MELLITUS

Glimepiride is a sulphonylurea agent that stimulates insulin release f rom pancreatic beta-cells and may net via extrapancreatic mechanisms. It is administered once daily to patients with type 2 (non-insulin-dep endent) 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 e ffects of glimepiride occur in the first 4 hours after the dose. Glime piride has fewer and less severe effects on cardiovascular variables t han glibenclamide (glyburide). Pharmacokinetics are mainly unaltered i n elderly patients or those with renal or liver disease. Few drug inte ractions with glimepiride have been documented. In patients with type 2 diabetes, glimepiride has an effective dosage range of 0.5 to 8 mg/d ay, 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 reduc e blood glucose more rapidly than glipizide over the first few weeks o f treatment. Glimepiride and gliclazide were compared in patients with good glycaemic control at baseline in a 14-week study that noted no d ifferences between their effects. Glimepiride plus insulin was as effe ctive as insulin plus placebo in helping patients with secondary sulph onylurea failure to reach a fasting blood glucose target level of less than or equal to 7.8 mmol/L, although lower insulin dosages and more rapid effects on glycemia were seen with glimepiride. Although glimepi ride monotherapy was generally well tolerated, hypoglycaemia occured i n 10 to 20% of patients treated for less than or equal to 1 year and g reater than or equal to 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, particular ly in the first month of treatment. Dosage is usually started at 1 mg/ day, titrated to glycaemia control at 1- to 2-week intervals to a usua l dosage range of 1 to 4 mg/day (maximum 6 mg/day in the UK or 8 mg/da y in the US). Conclusions. Glimepiride is a conveniently administered alternative to other sulphonylureas in patients with type 2 diabetes m ellitus not well controlled by diet alone. Its possible tolerability a dvantages and use in combination with other oral antidiabetic drugs re quire further study. Glimepiride is also reported to reduce exogenous insulin requirements in patients with secondary sulphonylurea failure when administered in combination with insulin.