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 diabeti...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.展开更多
Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized cont...Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.展开更多
文摘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.
文摘Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.
