Compared to glibenclamide, repaglinide treatment results in a more rapid fall in glucose level and beta-cell secretion after glucose stimulation.
BACKGROUND
The more rapid onset of action and the shorter half-life of repaglinide may reduce the post-load glucose excursion and limit sustained insulin secretion compared to sulphonylurea (SU) derivatives.


METHODS
We studied 12 patients with type 2 diabetes (age 62 +/- 2 years, BMI 28.3 +/- 1.3 kg m(-2), HbA1c 6.7 +/- 0.2%) on SU monotherapy at submaximal dose. Patients were treated for 3 weeks with repaglinide or glibenclamide in a randomized, crossover trial. At the end of each treatment period, patients underwent a 60-min hyperglycaemic clamp (glucose 12 mmol L(-1)) followed by 4-h observation (60-300 min) with frequent blood sampling for determination of glucose, insulin, proinsulin and C-peptide levels. Before the clamp (5 min for repaglinide, 30 min for glibenclamide), patients ingested their usual morning drug dose.


RESULTS
After the end of the hyperglycaemic clamp, mean plasma glucose fell to a level of 5 mmol L(-1) after approximately 150 min with repaglinide, and after approximately 190 min with glibenclamide. While initially quite similar, in the period from 240 to 300 min, insulin, proinsulin and C-peptide levels were lower during repaglinide treatment (insulin 133 +/- 20 vs 153 +/- 25 pmol L(-1) (P < 0.05), proinsulin 14 +/- 3 vs 19 +/- 4 pmol L(-1) (P = 0.06) and C-peptide 0.81 +/- 0.19 vs 1.14 +/- 0.18 nmol L(-1) (P = 0.05) for repaglinide vs glibenclamide, respectively).


CONCLUSIONS
Following glucose stimulation, plasma glucose levels, and insulin concentration decrease more rapidly after repaglinide treatment than after glibenclamide. Proinsulin and C-peptide secretion tended to fall more rapidly as well. These findings are consistent with a more rapid onset and shorter duration of beta-cell stimulation associated with repaglinide.
Abbink
Evertine J
EJ
Department of Internal Medicine, University Medical Centre, Nijmegen, The Netherlands.
van der Wal
Pieter S
PS
Sweep
C G J Fred
CG
Smits
Paul
P
Tack
Cees J
CJ
D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D002219:Carbamates / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D011384:Proinsulin / Q000097:blood / Q000378:metabolism; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; C072379:repaglinide; D011384:Proinsulin; D005947:Glucose; D005905:Glyburide