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Item
#6
Control
of Postprandial Hyperglycemia Using Short Acting Insulin Secretagogues
Timing
is critical in the optimal use of short-acting insulin secretagogues
This
study was designed to compare the efficacy of acute premeal
administration of glipizide versus nateglinide in
controlling postprandial hyperglycemia in subjects with
non-insulin-requiring type 2 diabetes.
A
total of 20 subjects (10 female, 10 male) with
non-insulin-requiring type 2 diabetes were admitted
overnight to the General Clinical Research Center on four
occasions. In random order, 10 mg glipizide (30 min premeal),
120 mg nateglinide (15 min premeal), 10 mg glipizide plus
nateglinide (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 glucose, insulin, and C-peptide at -0.05, 0, 0.5, 1, 2,
3, and 4 h relative to the meal.
The
subjects were aged 56 ± 2 years and were moderately obese
(BMI 31 ± 1 kg/m2), with a mean HbA1c
of 7.4 ± 0.4%. The peak postprandial glucose excursion above
baseline was higher with placebo than glipizide, nateglinide, or
glipizide plus nateglinide. The area under the curve for
the glucose excursion above baseline was also higher with placebo
compared with glipizide, nateglinide (9.7 ± 2
mmol/h · l, P = 0.004), or glipizide plus
nateglinide (5.6 ± 2.2 mmol/h · l, P < 0.001).
Peak and integrated glucose excursions did not differ significantly
between glipizide and nateglinide. However, by 4 h
postmeal, plasma glucose levels were significantly higher with
nateglinide compared with the premeal baseline and compared
with the 4-h postprandial glucose level after
administration of glipizide. Integrated postprandial insulin
levels were higher with glipizide than nateglinide. Early insulin
secretion, as measured by insulin levels at 30 min
postmeal, did not differ between glipizide and nateglinide.
From
the results it was concluded that, acute premeal administration of
nateglinide or glipizide has equal efficacy in controlling
post breakfast hyperglycemia in type 2 diabetes when each
drug is administered at the optimum time before the meal.
Glipizide causes a more pronounced and sustained postmeal
insulin secretory response compared with nateglinide.
Glipizide facilitates the return to near-fasting glucose
levels at 4 h postmeal, but with the possible risk of
increased frequency of postmeal hypoglycemia in drug-naive
patients.
The
clinical decision to use glipizide versus nateglinide
should be based on factors other than the control of
postprandial hyperglycemia in type 2 diabetes. Diabetes
Care 25:2147-2152, 2002
===========================
DID
YOU KNOW:
Diabetes-related
hospitalizations accounted for 13.9 million hospital days in 1997. The
mean length of stay was 5.4 days (American Diabetes Association,
1998).
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