A 1-year multicenter randomized double-blind comparison of repaglinide andglyburide for the treatment of type 2 diabetes

OBJECTIVE - Repaglinide is a newly developed oral blood glucose-lowering ag ent that exerts its effect by stimulating insulin secretion. This multicent er study was designed to compare the efficacy and safety of this drug with glyburide in a 1-year randomized double-blind study of outpatients with typ e 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 424 subjects (154 women, 270 men) participated and had the following characteristics: age, 61 +/- 9 years; du ration of diabetes, 8 years (range 0.5-35); BMI, 28.3 +/- 3.5 kg/m(2); HbA( 1c), 7.1 +/- 1.4%; and fasting plasma glucose, 10.8 +/- 3.1 mmol/l. The maj ority of the subjects (91%) were previously treated with sulfonyl-urea, alo ne or in combination with metformin. The patients were randomized to a 2:I ratio of repaglinide (0.5-4 mg t.i.d.) or glyburide (1.75-10.5 mg daily) tr eatment. The study protocol included a screening visit to assess patient el igibility; a titration period of 6-8 weeks, during which the dosages of rep aglinide and glyburide were optimized; and a subsequent 12-month treatment period on fixed, optimal dosages. RESULTS - The trial was completed by 320 subjects, 211 (74%) in the repagli nide and 109 (78%) in the glyburide group. HbA(1c) initially decreased in b oth groups and then increased during the second half-year of the maintenanc e period to a similar extent in the repaglinide and glyburide subjects (0.5 8 and 0.45% vs. at screening, respectively). In the small group of subjects who previously controlled their condition with diet only (n = 37), a susta ined improvement of metabolic control could be observed with both drugs, wh ich was slightly better with glyburide than with repaglinide (Delta HbA(1c) -2.4 vs. -1.0%; P < 0.05). The same trends were seen with fasting plasma g lucose. There were no changes in serum lipids. Over the course of the study 15% of the repaglinide-treated and 13% of glyburide-treated subjects withd rew due to adverse events, mostly hyperglycemia. No differences in adverse events between both drugs were reported. There were no differences in incid ences of hypoglycemia. CONCLUSIONS - Repaglinide is a safe and efficacious oral blood glucose-lowe ring agent, with a potency similar to that of glyburide. Its rapid onset of action and hepatic clearance allows meal-related administration, including in subjects with impaired kidney function.