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.