Effects of long-term monotherapy with glimepiride vs glibenclamide on glycemic control and macrovascular events in Japanese Type 2 diabetic patients

Abstract

We investigated whether long-term glimepiride (GP) monotherapy improves insulin resistance and exerts a beneficial effect on beta cell function , as compared with glibenclamide (GC). One hundred Japanese Type 2 diabetic patients were randomly assigned to the GP (n = 50) or the GC (n = 50) group. During a 5-year monitoring period , patients received the indicated SU mono-therapy, while changes in SU doses were allowed as needed to maintain HbA1C below 7.0%. The GC group, in parallel with fasting insulin, showed a rapid homeostatic model assessment (HOMA)-R increase and maintained a high HOMA-R level. In contrast, HOMA-R in the GP group decreased continuously, from 2.9 at ba-seline to 1.8 at study completion. In the GC group, HOMA-b was markedly increased in the first 6 months, then gradually decreased through 18 months. While the HOMA-β elevation in the GP group was more moderate than that in the GC group, HOMA-β levels were maintained with a slight decrease. The cumulative macrovascu-lar disease outcome was 1 for the GP and 7 for the GC group, showing a significant difference. These results suggest that glimepiride mono-therapy markedly improved HOMA-R with moderate insulin stimulation, which may account for the difference in macrovascular disease development as compared with the group receiving glibenclamide.