CLINICAL PROFILE OF GLIMEPIRIDE

In order to achieve appropriate blood glucose control, the treatment of non-insulin dependent (NIDDM) Type II diabetes usually starts with diet and exercise. If this still results in insufficient metabolic control, oral hypoglycaemic drugs or insulin are added to the non-pharmacological measures. Sulphonylureas have been used successfully as oral hypoglycaemic agents since the 1950s but there are aspects where medication could be better adjusted to the patients' needs. Preclinical investigations on animals and in vitro studies with glimepiride (HOE490), a new sulphonylurea, suggested some benefit over sulphonylureas currently available, including lower dosage, rapid onset and long duration of action, lower insulin and C-peptide levels, possibly due to less stimulation of insulin secretion and more pronounced extrapancreatic effects. The clinical relevance of these findings were studied in clinical trials. 19 phase II and 4 phase III clinical studies, in a total of about 3750 Type II diabetic patients, established efficacy and safety of glimepiride in comparison to placebo and glibenclamide and showed its therapeutic value. 1 mg per day induced a marked blood glucose reduction (FPG 2.4 mmol/l; HbA(1c) 1.2%) which could be enhanced by increasing the dose to the maximum effective 4 and 8 mg daily. In patients, glimepiride had a more rapid onset of action than glibenclamide, with a long duration of action. Glimepiride achieved metabolic control with the lowest dose (1-8 mg daily) of all the sulphonylureas. In addition, it maintained a more physiological regulation of insulin secretion than glibenclamide during physical exercise, suggesting that there may be less risk of hypoglycaemia with glimepiride. Large phase III studies were designed to characterise the product under conditions which were to be as close as possible to every-day life oral therapy of Type II diabetes. These long-term, glibenclamide-controlled studies showed that equivalent metabolic control was achieved with a dose range of 1-8 mg glimepiride given once daily and 2.5-20 mg glibenclamide daily (given as divided dose at the higher dose levels). This equivalent metabolic control was achieved with lower insulin concentrations (median difference: -0.92 mu U/ml; P = 0.04) and C-peptide (median difference: -0.14 ng/ml; P=0.03) with glimepiride. Glimepiride was well tolerated and fewer episodes of hypoglycaemia were observed in the glimepiride group than in the glibenclamide group. In conclusion, glimepiride showed a number of improvements over currently available sulphonylureas that may provide clinical benefit to patients with NIDDM.