Effect of repaglinide and gliclazide on postprandial control of endogenous glucose production

The effect of repaglinide and gliclazide on postmeal suppression of endogenous glucose production (EGP) has been studied using a variable-rate tracer methodology. Groups of age-, sex-, and weight-matched type 2 diabetic subjects randomized to gliclazide or repaglinide were studied after ingesting a standard mixed meal (550 kcal; 67% carbohydrate, 19% fat, 14% protein). Plasma glucose profiles were similar in each group and markedly different from that of a nondiabetic control group. Endogenous glucose production was similar basally (3.01 +/- 0.30 vs 3.06 +/- 0.19 mg/kg per minute, gliclazide and repaglinide, respectively). After glucose ingestion, EGP declined rapidly in both the groups until 30 minutes and the greatest suppression was reached earlier in the repaglinide group [0.88 mg/kg per minute at 120 minutes vs 0.77 mg/kg per minute at 210 minutes in gliclazide group (P < .05); median time, 85 vs 195 minutes, respectively (P < .05)]. The area under the curve (30-150) for EGP was significantly greater in the gliclazide group than in the nondiabetic control group (109 +/- 11 vs 198 +/- 22 mg/kg per min 2 ; P > .02) but not significantly different in the repaglinide group (153 +/- 25 mg/kg per min 2 ; P = .17). Repaglinide has minimal physiological advantage over gliclazide, but both therapies for type 2 diabetes fall far short of correcting the endocrine and metabolic abnormalities.