Enhancement of early- and late-phase insulin secretion and insulin sensitivity by the combination of repaglinide and metformin in type 2 diabetes mellitus.
The effects of a combination of repaglinide and metformin on the insulin secretion pattern and insulin sensitivity were studied in a fixed-dose, open-label, placebo-controlled cross-over study. Eleven patients with T2 DM were allocated in random order to treatment with placebo or repaglinide (1 mg pre-meal 3 x/day) in combination with metformin (2550 mg/day) for one-week periods of each. At the end of each period a hyperglycaemic (HC) and a euglycaemic clamp (EC) were performed. Both early (0 - 10 min) and late (25 - 180 min) phases of insulin secretion were significantly increased during HC with repaglinide compared to placebo (263.3 +/- 133.1 vs. 443.6 +/- 138.5 pmol/l/10 min, p = 0.008 and 18 750.9 +/- 5936.4 vs. 34 508.65 +/- 9234.0 pmol/l/25 - 180 min; p = 0.008). The C-peptide concentrations under steady-state conditions were lower in EC with placebo than with repaglinide (p = 0.014). When euglycaemia was achieved in EC, the C-peptide concentrations decreased from hyperglycaemic to normoglycaemic values in the presence of repaglinide but remained higher than after placebo. The insulin sensitivity index (ISI) was increased by 35 % after 1 week of combination therapy with repaglinide plus metformin (1.11 +/- 0.03 x 10 (2) vs. 0.83 +/- 0.21 x 10 (2) mg x kg (-1) body weight x min (-1) x pmol (-1) x l, respectively; p = 0.033). Repaglinide increased early and late phases of insulin responses in HC, without markedly enhancing insulin secretion in euglycaemia. Repaglinide in combination with metformin produced a significant enhancement of ISI, suggesting a synergistic effect on insulin sensitivity.
Rudovich
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NN
Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
Leyck Dieken
M G
MG
Rochlitz
H
H
Pfeiffer
A F H
AF
D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage*; D015331:Cohort Studies; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D010919:Placebos; D013997:Time Factors
D002096:C-Peptide; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D010919:Placebos; C072379:repaglinide; D008687:Metformin