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

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Journal of Diabetes Mellitus 2014年第1期4卷 33-37页

作者： Hirohisa Onuma Kouichi Inukai Masaki Watanabe yoshikazu sumitani Toshio Hosaka Hitoshi Ishida Third Department of Internal Medicine Kyorin University School of Medicine Tokyo Japan Watanabe Medical Clinic Hiroshima Japan

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.

关键词： Glibenclamide Glimepiride Macrovascular Events HOMA-R/β

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Clinical Characteristics of Japanese Type 2 Diabetic Patients Responsive to Sitagliptin

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Journal of Diabetes Mellitus 2014年第3期4卷 172-178页

作者： Kouichi Inukai Takumi Hirata Takashi Sumita Masaki Watanabe Yuichi Ikegami Daisuke Ito Susumu Kurihara Nobuyuki Yasukawa Jiro Morimoto Nobuki Takata Kenta Kanazawa Tamotsu Neda yoshikazu sumitani Kiyoaki Inoue Yuichi Noguchi Toshio Hosaka Hitoshi Ishida Shigehiro Katayama Department of Internal Medicine Saitama Social Insurance Hospital Saitama Japan Division of Endocrinology and Diabetes Saitama Medical University Saitama Japan Foundation for Biomedical Research and Innovation Hyogo Japan Sakado Central Hospital Saitama Japan Third Department of Internal Medicine Division of Diabetes Endocrinology and Metabolism Kyorin University School of Medicine Tokyo Japan Watanabe Medical Clinic Hiroshima Japan

Japanese type 2 diabetic patients were treated with sitagliptin to evaluate the efficacy of this agent, and also to investigate the clinical characteristics of those who responded to sitagliptin. In total, 1001 diabetic patients, inadequately controlled (HbA1c ≥ 6.5%) with oral hypoglycemic agents (OHA) other than DPP-4 inhibitors or with diet and exercise only, were enrolled. We added 50mg of sitagliptin to the therapeutic regimens of 410 patients including 68 OHA naive patients, while the other 591 patients were switched from a single OHA to 50 mg of sitagliptin. After 6 months, glycemic control was significantly improved due to both reduced insulin resistance, as demonstrated by a significant HOMA-R reduction, and recovery of pancreatic β cell function, as assessed by HOMA-β and the proinsulin/insulin (PI/I) ratio. In the bivariable analysis, a good response, defined as an HbA1c reduction during the 6 months of at least 0.9%, was associated with high HbA1c and PI/I at baseline and combination treatments with sulfonylurea, biguanide and α-glucosidase inhibitors, but not with obesity. On the other hand, in the multivariable regression analysis, only high baseline HbA1c and combination treatment with anα-glucosidase inhibitor were significantly associated with a good response to sitagliptin. In patients with type 2 diabetes, the addition of sitagliptin or switching from another OHA to this agent achieved an HbA1c reduction without overloading β cells. In particular, we suggest that a good response to sitagliptin can be expected when this agent is combined with an α-glucosidase inhibitor (UMIN No. #000014157).

关键词： Sitagliptin Type 2 Diabetes DPP-4 Inhibitors

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