Repaglinide/Troglitazone Combination Therapy

he pathogenesis of type 2 diabetesmay involve dual metabolic defects ofinadequate -cell function as well asreduced sensitivity of insulin target tis-sues. Patients typically show a decliningresponse to oral hypoglycemic agents overtime. The recent availability of new oralagents with varying mechanisms of actionhas increased the possibility of meaningfulcombination therapy that can be superiorto the use of these agents as monotherapy.Several studies have reported improvedglycemic control with such combinationtherapy (1–3).Repaglinide is the first oral agent of themeglitinide class to become available for thetreatment of type 2 diabetes (4) and has amechanism of -cell stimulation that differsfrom sulfonylureas (5). Repaglinide is chem-ically unrelated to sulfonylureas or any othercurrently available class of oral hypoglycemicagents (6). Rapid absorption and clearance ofrepaglinide make this agent a suitable choicefor the management of meal-related bloodglucose surges.Troglitazone is a thiazolidinedione,which is a class of drugs that improvesinsulin sensitivity in peripheral tissues. Byincreasing both the supply and physiologicaleffectiveness of circulating insulin in patientswith type 2 diabetes, such a secretagogue/sensitizer combination therapy regimen maybe an improvement on the efficacy of eitheragent used as a monotherapy. Repaglinideoffers an unusually short elimination half-life( 1 h) and meal-time dosing administration,which results in an insulin stimulation that ismaximal during postprandial periods whenit is most needed, unlike even short-actingsulfonylureas. The safety profile of repaglin-ide is a key factor to weigh when combiningtreatments that may each contribute toadverse events. Because repaglinide has ashorter duration of action than sulfonyl-ureas and offers the simple option of skip-ping the dose for missed meals, repaglinidemay involve less risk of hypoglycemicepisodes than other available secretagogues.This clinical trial was designed to com-pare the efficacy and safety of a combina-tion of repaglinide/troglitazone, repaglinidemonotherapy, and troglitazone monother-apy in the glycemic management of type 2diabetes in patients who had previouslyshown an inadequate glycemic response tomonotherapy with either sulfonylureas,acarbose, or metformin.