Repaglinide - Prandial glucose regulator: A new class of oral antidiabeticdrugs

The highest demand on insulin secretion occurs in connection with meals. In normal people, following a meal, the insulin secretion increases rapidly, reaching peak concentration in the blood within an hour. The mealtime insul in response in patients with Type 2 diabetes is blunted and delayed, wherea s basal levels often remain within the normal range (albeit: at elevated fa sting glucose levels). Restoration of the insulin secretion pattern at meal times (prandial phase)-without stimulating insulin secretion in the 'postab sorptive' phase-is the rationale for the development of 'prandial glucose r egulators', drugs that are characterized by a very rapid onset and shout du ration of action in stimulating insulin secretion. Repaglinide, a carbamoyl methyl benzoic acid (CMBA) derivative is the first such compound, which rec ently has become available for clinical use. Repaglinide is very rapidly ab sorbed (t(max) less than 1 hour) with a t(1) of less than one hour. Further more, repaglinide is inactivated in the liver and more than 90 % excreted v ia the bile. The implications of tailoring repaglinide treatment to meals w ere examined in a study where repaglinide tvas dosed either morning and eve ning, or with each main meal (i.e. breakfast, lunch, dinner), with the tota l daily dose of repaglinide being identical. The mealtime dosing caused a s ignificant improvement in both fasting and 24-hour glucose profiles,as well as a significant decrease in HbA(1c). In other studies, repaglinide caused a decrease of 5.8 mmoI.l(-1) in peak postprandial glucose levels, and a de crease of 3.1 mmol.l(-1) in fasting levels with a reduction in HbA(1c) of 1 .8 % compared with placebo. In comparative studies with either sulphonylure a or metformin, repaglinide caused similar or improved control (i.e. HbA(1c ), mean glucose levels) and the drug was well tolerated (e.g, reported gast rointestinal side-effects were more than halved when patients were switched from metformin to repaglinide). A hallmark of repaglinide treatment is tha t this medication follows the eating pattern, and not vice versa. Hence the risk of developing severe hypoglycaemia (BG less than or equal to 2.5 mmol .l(-1)) in connection with flexible lifestyles should be reduced. This conc ept was examined in a study in which patients well controlled on repaglinid e skipped their lunch on one occasion. When a meal (i.e. lunch) was skipped -so tvas the repaglinide dose, whereas in the comparative group on glibencl amide the recommended morning and evening doses were taken. Twenty-four per cent of the patients in the glibenclamide group developed severe hypoglyca emia, whereas no hypoglycaemic events occurred in the group receiving repag linide. However, in long-term studies the overall prevalence of hypoglycaem ia was similar to that found with other insulin secretagogues. In summary, current evidence shows that the concept of prandial glucose regulation offe rs good long-term glycaemic control combined with a low risk of severe hypo glycaemia with missed meals. The concept should meet the needs of Type 2 di abetic patients, allowing flexibility in their lifestyle. (C) 1998 John Wil ey & Sons, Ltd.