A review of clinical experience with the prandial glucose regulator, repaglinide, in the treatment of type 2 diabetes.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 100897346 Publication Model: Print Cited Medium: Print ISSN: 1465-6566 (Print) Linking ISSN: 14656566 NLM ISO Abbreviation: Expert Opin Pharmacother Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: London : Ashley Publications, c1999-

Blood Glucose/*metabolism ; Carbamates/*therapeutic use ; Diabetes Mellitus, Type 2/*drug therapy ; Hypoglycemic Agents/*therapeutic use ; Piperidines/*therapeutic use; Carbamates/adverse effects ; Carbamates/pharmacology ; Clinical Trials as Topic ; Diabetes Mellitus, Type 2/blood ; Drug Therapy, Combination ; Humans ; Hypoglycemic Agents/adverse effects ; Hypoglycemic Agents/pharmacology ; Piperidines/adverse effects ; Piperidines/pharmacology ; Postprandial Period/physiology

Repaglinide is a novel insulin secretagogue that was developed as a prandial glucose regulator for the treatment of people with Type 2 diabetes mellitus. It is used flexibly, taken prior to meals, in order to limit subsequent postprandial blood glucose excursions as well as the dependent basal blood glucose concentration. In theory, the pharmacological profile of repaglinide is well suited for this role. Taken at mealtimes, its relatively rapid-onset and short-duration of action counteract a fundamental pathophysiological aspect of this disease: attenuation of the prandial insulin response. The predominantly hepatic elimination profile and a lack of drug-drug interactions with repaglinide are also properties well suited for patients with Type 2 diabetes. Importantly, the pharmacokinetic properties of repaglinide, are expected to reduce the risk of hypoglycaemia in comparison to the conventional insulin secretagogues (sulphonylureas). A reduced risk of hypoglycaemia carries the advantage that patients are not obliged to consume meals at regular intervals supplemented by snacks, so caloric restriction is feasible and lifestyle not compromised. These theoretical advantages have now been largely borne-out by clinical studies and empirical experience. Placebo-controlled studies have consistently demonstrated the antidiabetic efficacy of repaglinide, with improvements having been shown in all indicators of glycaemic control. Double-blind, active-comparator studies have shown repaglinide to have an antidiabetic efficacy that is at least equivalent to sulphonylureas, even when food intake and dosing intervals were controlled according to the requirements of sulphonylureas. Pooled data from these studies have shown that the risk of severe hypoglycaemia is reduced by 60% (p = 0.03) when repaglinide is used in preference to sulphonylureas. There is also evidence that the blood glucose threshold at which symptoms of hypoglycaemia are perceived by patients may be better preserved during treatment with repaglinide than with sulphonylureas. Studies examining flexible prandial dosing with repaglinide have shown that good glycaemic control and a low risk of hypoglycaemia are achievable goals that are independent of the meal (and, hence, dosing) pattern chosen by the patient. Furthermore, when used in this way, repaglinide has not been associated with weight gain. In combination therapy, repaglinide has been shown to act in synergy with both metformin and troglitazone. The possibility of a 'new' basal-bolus regimen combining repaglinide and exogenous (neutral protamine hagedorn) NPH insulin strategy has also been investigated.

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0 (Blood Glucose)
0 (Carbamates)
0 (Hypoglycemic Agents)
0 (Piperidines)
668Z8C33LU (repaglinide)

Date Created: 20010316 Date Completed: 20010405 Latest Revision: 20190915

20240627

10.1517/14656566.1.7.1455

11249478