Repaglinide--a new compound for the treatment of patients with type 2 diabetes.
Repaglinide is a new oral blood glucose lowering agent, a member of the carbamoylmethyl benzoic acid (CMBA) family. Its mechanism of action is partly similar to that of the sulphonylurea: the release of insulin from the pancreatic beta cells is stimulated by closure of ATP-dependent potassium channels. However, repaglinide regulates these channels via a different binding site on the beta cell than glibenclamide, and the drug does not cause insulin release in the absence of glucose, or during voltage-clamping. After oral administration the drug is rapidly absorbed and eliminated. It is therefore used in a meal-related dosing regimen; repaglinide is taken with each main meal. This meal-related use may give a more physiological mimick of daytime insulin requirement than once-daily or twice-daily use of sulphonylurea. Patients using repaglinide are less likely to develop hypoglycaemic symptoms when they miss or postpone a meal in comparison with patients on glibenclamide treatment. In long-term comparative phase 3 clinical studies it was found that repaglinide is equally effective in maintaining glycaemic control as existing sulphonylurea, but it gives significantly better control of postprandial blood glucose levels. Repaglinide can be used as monotherapy both in obese and non-obese type 2 diabetic patients, and is also very effective in combination with drugs like metformin or thiazolidines. Because of its excretion through liver and bile it is also an attractive drug for diabetic patients with diminished kidney function, especially the elderly diabetic. Although the overall incidence of hypoglycaemia was similar during use of repaglinide and of sulphonylurea, fewer serious hypoglycaemic episodes were observed in repaglinide-treated patients.
Wolffenbuttel
B H
BH
Dept. of Endocrinology and Metabolism, University Hospital Maastricht, The Netherlands. bwo@sint.azm.nl
D000284:Administration, Oral; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D002219:Carbamates / Q000737:chemistry / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005247:Feeding Behavior; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D007408:Intestinal Absorption; D008657:Metabolic Clearance Rate; D010880:Piperidines / Q000737:chemistry / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide