Beta-cell response during a meal test: a comparative study of incremental doses of repaglinide in type 2 diabetic patients.
OBJECTIVE
To assess the effects of incremental doses of repaglinide on postprandial insulin and glucose profiles after a standard 500-kcal test meal.


METHODS
Sixteen diet-treated Caucasians with type 2 diabetes (mean HbA(1c) 8.4%) were enrolled in this randomized, open-label, crossover trial. Subjects received 0.5, 1, 2, and 4 mg repaglinide or placebo in a random fashion, followed by a standard 500-kcal test meal on 5 separate study days, 1 week apart.


RESULTS
The insulinogenic index (DeltaI30/DeltaG30) and insulin area under the curve (AUC) from 0 to 30 min (AUC(0-30)) were higher with the 4-mg drug dose compared with the two lower doses and with 2 mg compared with 0.5 mg. On subgroup analysis, the incremental insulin responses were apparent only in the fasting plasma glucose (FPG) < 9-mmol/l subgroup of subjects and not in the FPG >9-mmol/l subgroup. There was a significant dose-related increase in the late postprandial insulin secretion (insulin AUC(120-240)), which resulted in hypoglycemia in four subjects. Proinsulin-to-insulin ratios at 30 and 60 min improved with increasing doses of repaglinide; higher drug doses (2 and 4 mg) were more effective than the 0.5- and 1-mg doses.


CONCLUSIONS
Significant dose-related increases in early insulin secretion were found only in less advanced diabetic subjects. In advanced diabetic patients, only the maximum dose (4 mg) was significant compared with placebo. Better proinsulin-to-insulin processing was noted with increasing drug doses.
Cozma
Lawrence S
LS
Diabetes Research Unit, Academic Centre, Llandough Hospital, Penlan Road, Penarth, Cardiff CF64 2XX, Wales, U.K. sl.cozma@ntlworld.com
Luzio
Stephen D
SD
Dunseath
Gareth J
GJ
Underwood
Paul M
PM
Owens
David R
DR
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D002219:Carbamates / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004435:Eating; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D019518:Postprandial Period
D001786:Blood Glucose; D002096:C-Peptide; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; C072379:repaglinide