Control of postprandial XXXX : optimal use of short-acting insulin secretagogues.

@entity1 @entity6 @entity4053 @entity15506 @entity6347 @entity4854 @entity413
OBJECTIVE: This study was designed to compare the efficacy of acute premeal administration of @entity15506 versus @entity6347 in controlling postprandial @entity4854 in subjects with non-insulin-requiring type 2 @entity6 . RESEARCH DESIGN AND METHODS: A total of 20 subjects (10 female, 10 male) with non-insulin-requiring type 2 @entity6 were admitted overnight to the General Clinical Research Center on four occasions. In random order, 10 mg @entity15506 (30 min premeal), 120 mg @entity6347 (15 min premeal), 10 mg @entity15506 plus @entity6347 (30 and 15 min premeal, respectively), or placebo pills (30 and 15 min premeal) were administered in a double-blind fashion before a standardized breakfast. Blood was drawn for analysis of @entity413 , insulin, and C-peptide at -0.05, 0, 0.5, 1, 2, 3, and 4 h relative to the meal. RESULTS: The subjects were aged 56 +/- 2 years and were moderately obese (BMI 31 +/- 1 kg/m(2)), with a mean HbA(1c) of 7.4 +/- 0.4%. The peak postprandial @entity413 excursion above baseline was higher with placebo (6.1 +/- 0.5 mmol/l) than @entity15506 (4.3 +/- 0.6 mmol/l, P = 0.002), @entity6347 (4.2 +/- 0.4 mmol/l, P = 0.001), or @entity15506 plus @entity6347 (4.1 +/- 0.5 mmol/l, P = 0.001). The area under the curve for the @entity413 excursion above baseline was also higher with placebo (14.1 +/- 1.8 mmol/h. l) compared with @entity15506 (6.9 +/- 2.4 mmol/h. l, P = 0.002), @entity6347 (9.7 +/- 2 mmol/h. l, P = 0.004), or @entity15506 plus @entity6347 (5.6 +/- 2.2 mmol/h. l, P < 0.001). Peak and integrated @entity413 excursions did not differ significantly between @entity15506 and @entity6347 . However, by 4 h postmeal, plasma @entity413 levels were significantly higher with @entity6347 (9 +/- 0.9 mmol/l) compared with the premeal baseline (7.8 +/- 0.6 mmol/l, P = 0.04) and compared with the 4-h postprandial @entity413 level after administration of @entity15506 (7.6 +/- 0.6 mmol/l, P = 0.02). Integrated postprandial insulin levels were higher with @entity15506 (1,556 +/- 349 pmol/h. l) than @entity6347 (1,364 +/- 231 pmol/h. l; P = 0.03). Early insulin secretion, as measured by insulin levels at 30 min postmeal, did not differ between @entity15506 and @entity6347 . CONCLUSIONS: Acute premeal administration of @entity6347 or @entity15506 has equal efficacy in controlling postbreakfast @entity4854 in type 2 @entity6 when each drug is administered at the optimum time before the meal. @entity15506 causes a more pronounced and sustained postmeal insulin secretory response compared with @entity6347 . @entity15506 facilitates the return to near-fasting @entity413 levels at 4 h postmeal, but with the possible risk of increased frequency of postmeal @entity4053 in drug-naive @entity1 . The clinical decision to use @entity15506 versus @entity6347 should be based on factors other than the control of postprandial @entity4854 in type 2 @entity6 .
