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 monotherapy, 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 baseline 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 macrovascular disease outcome was 1 for the GP and 7 for the GC group, showing a significant difference. These results suggest that glimepiride monotherapy 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.
Highlights
Glimepiride (GP), a sulfonylurea (SU) derivative, has been widely used in the treatment of Type 2 diabetic patients in Europe and Asia
As to these SUs, we previously reported that insulin resistance was significantly reduced by 6 months without improvements in glycemic control by switching from 2nd generation SUs to glimepiride [4]
We demonstrated that long-term glimepiride monotherapy improves homeostatic model assessment (HOMA)-R and exerts a decreased risk for macrovascular events, as compared with glibenclamide
Summary
Glimepiride (GP), a sulfonylurea (SU) derivative, has been widely used in the treatment of Type 2 diabetic patients in Europe and Asia. This agent has a mild effect on insulin secretion, with a hypoglycemic effect equivalent to that of glibenclamide (GC) [1]. This SU is anticipated to have additional extrapancreatic effects, such that glimepiride has been designated as a 3rd generation SU. Recent clinical studies showed that glimepiride enhances insulin sensitivity, though it stimulates less insulin secretion than conventional 2nd generation SUs [2,3,4]. In vitro experiments demonstrated glimepiride to enhance insulin sensitivity via activation of insulin mediated glycogen synthesis [5], enhanced glucose uptake [6] and activation of peroxisome proliferator-activated receptor (PPAR) g transcriptional activity [7,8,9]
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