Repaglinide

A Review of its Therapeutic Use in Type 2 Diabetes Mellitus

Culy, Christine R.
Jarvis, Blair

Adid International Limited, Auckland, New Zealand

Various sections of the manuscript reviewed by:R.B. Goldberg, Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida, USA; G.D. Johnston, Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Belfast, Northern Ireland; R. Landgraf, Diabetes Center, Department of Internal Medicine, University of Munich, Germany; W.J. Malaisse, Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium; T.C. Marbury, Orlando Clinical Research Center, Orlando, Florida, USA; A.D. Mooradian, Department of Internal Medicine, St Louis University Medical School, St Louis, Missouri, USA; R. Moses, Department of Biomedical Science, University of Wollongong, Wollongong, New South Wales, Australia.

Correspondence: Christine R. Culy, Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand. E-mail: [email protected]

Drugs 61(11):p 1625-1660, 2001.

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new class of oral antidiabetic agents designed to normalise postprandial glucose excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas, repaglinide reduces blood glucose by stimulating insulin release from pancreatic β-cells, but differs from these and other antidiabetic agents in its structure, binding profile, duration of action and mode of excretion.

In clinical trials of up to 1-year's duration, repaglinide maintained or improved glycaemic control in patients with type 2 diabetes mellitus. In comparative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar glycaemic control to that in patients receiving glibenclamide (glyburide) ≤15 mg/day and greater control than patients receiving glipizide ≤15 mg/day. Changes from baseline in glycosylated haemoglobin and fasting blood glucose levels were similar between patients receiving repaglinide and glibenclamide in all studies; however, repaglinide was slightly better than glibenclamide in reducing postprandial blood glucose in 1 short term study (n = 192).

Patients can vary their meal timetable with repaglinide: the glucose-lowering efficacy of repaglinide was similar for patients consuming 2, 3 or 4 meals a day.

Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin (NPH) given at bedtime.

In 1-year trials, the most common adverse events reported in repaglinide recipients (n = 1228) were hypoglycaemia (16%), upper respiratory tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall incidence of hypoglycaemia was similar to that recorded in patients receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea 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 available treatments for type 2 diabetes mellitus. Preprandial repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various sulphonylureas 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 repaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by diet or exercise alone, or as an adjunct in patients whose glucose levels are inadequately controlled on metformin alone.