摘要：

Synopsis Glimepiride is a sulphonylurea agent that stimulates insulin release from pancreatic β-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 ≤ 7.8mmol/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 ≤ 1 year and ≥ 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). Conclusions. 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. Pharmacodynamic Properties Glimepiride acts at ATP-sensitive potassium (K atp ) channels on pancreatic β-cells to promote insulin release. It binds to 65kD protein on β-cells, which appears to be a part of the same sulphonylurea receptor that binds glibenclamide. Glimepiride decreases gluco-/hexokinase binding to porin proteins and increases expression of glucokinase mRNA and the glucose transporter GLUT2 in pancreatic cells in vitro . The maximum effects of glimepiride (relative to placebo) on blood glucose and insulin levels in patients with type 2 (non-insulin-dependent) diabetes mellitus appear during the first 4 hours after the dose. Over this 4-hour period, greater reductions in blood glucose occurred on the 4th day of treatment with glimepiride 2 mg/day than glibenclamide 10.5 mg/day (6.0 vs 5.1 mmol/L, p < 0.05). A weak relationship between blood glucose response and dosage was seen in patients with type 2 diabetes receiving glimepiride 1 to 8 mg/day. Glimepiride increased or did not change glucose utilisation rates in patients with type 2 diabetes in euglycaemic hyperinsulinaemic clamp studies. Glimepiride was also associated with greater reductions in insulinaemia than glibenclamide during exercise, despite similar reductions in blood glucose. Glimepiride may be given before or with breakfast, with equivalent effect. Effects of glimepiride on extrapancreatic mechanisms appear to be similar to those of other sulphonylureas. The drug appears to act within peripheral cell

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