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Repaglinide Improves Insulin Secretion More Effectively Than Glimepiride in Patients With Type 2 Diabetes

Repaglinide is more efficient in increasing insulin action and insulin secretion mediated by glucose or induced by a mixed meal than is glimepiride, according to evidence gathered recently by a team of researchers from Naples, Italy.

Fourteen patients between 50 and 80 years of age, all with type 2 diabetes, participated in the randomised, cross-over parallel group trial comparing the effects of repaglinide and glimepiride. The 9 men and 5 women were all naïve for diet treatment.

The patients were started on a hypocaloric diet during the 2-week run-in period after enrolment, following which they were randomly assigned for 4 weeks to repaglinide 1 mg twice a day before lunch and dinner, or to glimepiride 2 mg once a day before lunch, while maintaining their diet.

Patients were then prescribed a standard meal test with a caloric value of 500 Kcal (55% carbohydrate, 30% fat, 15% protein) and a hyperglycaemic clamp (intravenous bolus of 20% glucose over 1-2 minutes), after an overnight fast and with an interval of at least 24 hours between the tests. A wash-out period followed for 2 weeks before starting the cross-over treatment for another 4 weeks. Meal tests and hyperglycaemic clamps were then repeated in reverse order.

Sampling for glucose, insulin and C-peptide was performed throughout the glucose infusion. Patients received their medication orally 15 minutes before the meal test. Plasma glucose, insulin, total cholesterol, triglycerides and free fatty acids were obtained from venous blood samples at predetermined intervals after the meal.

At baseline, both treatments were responsible for important declines in fasting plasma glucose, total cholesterol and triglycerides levels.

During the hyperglycaemic clamp, incremental plasma insulin and C-peptide concentrations reached significantly higher values after repaglinide than with glimepiride administration at different study times. Steady state plasma insulin and C-peptide levels were also higher after repaglinide administration as were the incremental first and second phase of insulin secretion. Repaglinide resulted in a greater improvement in insulin action and amelioration of hepatic clearance than glimepiride.

During the meal test, repaglinide was associated with a more rapid onset of insulin secretion which reached a peak at 45 min in the repaglinide-treated patients compared to 60 min in the glimepiride-treated patients.

Only 3 patients treated with repaglinide experienced a mild episode of symptomatic hypoglycaemia while 2 patients treated by glimepiride reported such an event.

"Our study demonstrates that multiple daily doses of repaglinide are more efficient than glimepiride on improving glucose- and mixed meal-induced insulin secretion as well as on insulin action," conclude the authors.






Diabetes Metab 2004 Feb;30:1:81-9. "RepaglinIde is more efficient than glimepirIde on insulin secretion and post-prandial glucose excursions in patients with type 2 diabetes. A short term study"

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