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Compared to Glibenclamide, Repaglinide Causes Faster Drop in Glucose Levels following Hyperglycaemic Clamp: Presented at EASD

By Thomas S. May
Special to DG News

BUDAPEST, HUNGARY -- September 4, 2002 -- The fall in plasma glucose levels following glucose stimulation is more rapid after repaglinide than it is after glibencamide, according to research presented here yesterday, at the 38^th annual meeting of the European Association for the Study of Diabetes (EASD).

Repaglinide is a new type of insulin secretagogue, which has a similar mechanism of action to that of sulfonylurea (SU) derivatives, but has a different chemical structure.

A group of researchers led by Dr. Evertine Abbink of Nijmegen University Medical Centre, Nijmegen, The Netherlands, enrolled 12 patients with type 2 diabetes (age 62 ±3 yrs; BMI 28.3 ±1.3 kg/m2; HbA1c<8 percent) in a randomized crossover trial. Half of the patients were treated for a period of 3 weeks with glibenclamide first, then with repaglinide for the next 3 weeks. The other six patients were first given repaglinide for 3 weeks, then glibenclamide for the following 3 weeks.

At the end of each 3-week treatment period, patients underwent a 60-minute hyperglycaemic clamp (using 12 mmol/L of glucose) followed by 4 hours of observation with frequent blood sampling to determine glucose, insulin, pro-insulin, and C-peptide concentration. All patients ingested their usual morning drug dose before the clamp (5 min for repaglinide, 30 min for glibenclamide).

Plasma glucose levels decreased gradually after the glycaemic stimulation had been discontinued. Mean plasma glucose concentration fell to 5 mmol/L in approximately 210 minutes after repaglinide. After glibenclamide, the same level was reached in approximately 250 minutes. Mean plasma insulin concentration was lower in the period from 180 to 300 minutes after repaglinide than in the same period following glibenclamide (146 ± 25 vs 182 ± 26 pmol/L, p<0.05).

"The main advantage of repaglinide is that the blood glucose level after a glucose load returns to baseline value within a significantly shorter period of time than after treatment with glibenclamide," said Dr. Piet van der Wal, of Novo Nordisk Farma, The Netherlands, one of the co-authors of the study.

"Furthermore, we observed that the proinsulin secretion after drug administration and glucose load is shut down earlier during repaglinide treatment than during glibenclamide treatment," he added.

Dr. van der Wal also pointed out that repaglinide has been approved for treatment of patients with severe renal failure, because it is excreted via the hepatic route.

The study was funded by Novo Nordisk Farma, the manufacturer of repaglinide.

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