Repaglinide - A review of its therapeutic use in type 2 diabetes mellitus

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a n ew class of oral antidiabetic agents designed to normalise postprandial glu cose excursions in patients with type 2 diabetes mellitus. Like the sulphon ylureas, repaglinide reduces blood glucose by stimulating insulin release f rom pancreatic beta -cells, but differs from these and other antidiabetic a gents in its structure, binding profile, duration of action and mode of exc retion. In clinical trials of up to 1-year's duration, repaglinide maintained or im proved glycaemic control in patients with type 2 diabetes mellitus. In comp arative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar g lycaemic control to that in patients receiving glibenclamide (glyburide) le ss than or equal to 15 mg/day and greater control than patients receiving g lipizide less than or equal to 15 mg/day. Changes from baseline in glycosyl ated haemoglobin and fasting blood glucose levels were similar between pati ents receiving repaglinide and glibenclamide in all studies; however, repag linide was slightly better than glibenclamide in reducing postprandial bloo d glucose in 1 short term study (n = 192). Patients can vary their meat timetable with repaglinide: the glucose-loweri ng efficacy of repaglinide was similar for patients consuming 2, 3 or 4 mea ls a day. Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglit azone and pioglitazone, and intermediate-acting insulin (NPH) given at bedt ime. In 1-year trials, the most common adverse events reported in repaglinide re cipients (n = 1228) were hypoglycaemia (16%), upper respiratory tract infec tion (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall i ncidence of hypoglycaemia was similar to that recorded in patients receivin g glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the inci dence of serious hypoglycaemia appears to be slightly higher in sulphonylur ea recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving repaglinide was not increased when a meal was missed in 1 trial. In conclusion, repaglinide is a useful addition to the other currently avai lable treatments for type 2 diabetes mellitus. Preprandial. repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various su lphonylureas and is associated with a reduced risk of serious hypoglycaemia . It is well tolerated in a wide range of patients, including the elderly, even if a meal is missed. Furthermore, glycaemic control is improved when r epaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose bl ood glucose cannot be controlled by diet or exercise alone, or as an adjunc t in patients whose glucose levels are inadequately controlled on metformin alone.