Kutoh Eiji, Wada Asuka, Murayama Teruma, Takizawa Yui
Division of Clinical Research, Biomedical Center, 1-5-8-613 Komatsugawa, Edogawa-ku, Tokyo, 132-0034, Japan.
Division of Diabetes and Endocrinology, Department of Internal Medicine, Gyoda General Hospital, Saitama, Japan.
Drugs R D. 2017 Jun;17(2):313-320. doi: 10.1007/s40268-017-0179-7.
The aim of this study is to investigate canagliflozin as an initial therapy in type 2 diabetes mellitus and to explore the effects on metabolic parameters in relation to effects on glycemic control.
Treatment-naïve subjects with type 2 diabetes mellitus received canagliflozin 50-100 mg/day monotherapy. At 3 months, levels of glycemic and non-glycemic parameters were compared with those at baseline (n = 39). As a comparator, our previous data of baseline glycosylated hemoglobin (HbA)-matched treatment-naïve subjects with ipragliflozin 25-50 mg monotherapy (n = 27) were employed.
Significant reductions in HbA (from 9.96 to 8.33%), fasting blood glucose (-23.9%), homeostasis model assessment-R (HOMA-R, -33.5%), body mass index (-1.8%), and uric acid (UA, -5.2%) levels and significant increases in homeostasis model assessment-B (HOMA-B, 30.1%) levels were observed. Approximately one third of the subjects experienced certain adverse events. Similar results were obtained with ipragliflozin. Baseline levels of HbA, triglycerides, non-high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were chosen as significant contributing factors for the changes in HbA levels with canagliflzoin, while only baseline HbA levels were selected as such a factor with ipragliflozin. Significant positive correlations between the changes in HbA and changes in non-HDL-C (R = 0.3954) or between changes in HbA and changes in LDL-C (R = 0.4317) were observed with canagliflozin. With ipragliflozin, no such correlations were noted. No correlations between the changes in HbA and changes in body mass index were seen with both drugs.
These results suggest that (1) canagliflozin appears to offer clinically beneficial outcomes as an initial therapy in subjects with type 2 diabetes mellitus, although with certain adverse events. (2) Atherogenic cholesterols including non-HDL-C and LDL-C could be involved in the glycemic efficacy of canagliflozin. This was not the case with ipragliflozin. (3) Unexpectedly, weight reductions with canagliflozin are not associated with its glycemic efficacy.
本研究旨在探讨卡格列净作为2型糖尿病初始治疗药物的疗效，并探究其对代谢参数的影响以及与血糖控制效果的关系。
未经治疗的2型糖尿病患者接受卡格列净50 - 100毫克/天的单药治疗。3个月时，将血糖和非血糖参数水平与基线水平进行比较（n = 39）。作为对照，采用了我们之前关于基线糖化血红蛋白（HbA）匹配的未经治疗的依帕列净25 - 50毫克单药治疗受试者的数据（n = 27）。
观察到HbA水平显著降低（从9.96%降至8.33%）、空腹血糖降低（-23.9%）、稳态模型评估-胰岛素抵抗（HOMA-R，-33.5%）、体重指数降低（-1.8%）以及尿酸（UA，-5.2%）水平显著降低，同时稳态模型评估-胰岛β细胞功能（HOMA-B，30.1%）水平显著升高。约三分之一的受试者经历了某些不良事件。依帕列净也获得了类似结果。基线HbA、甘油三酯、非高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）水平被选为卡格列净治疗后HbA水平变化的显著影响因素，而依帕列净治疗时仅基线HbA水平被选为这样一个因素。卡格列净治疗后观察到HbA变化与非HDL-C变化之间存在显著正相关（R = 0.3954），以及HbA变化与LDL-C变化之间存在显著正相关（R = 0.4317）。使用依帕列净时，未观察到此类相关性。两种药物治疗后HbA变化与体重指数变化之间均未观察到相关性。
这些结果表明：（1）卡格列净作为2型糖尿病患者的初始治疗药物似乎能带来临床有益的结果，尽管存在某些不良事件。（2）包括非HDL-C和LDL-C在内的致动脉粥样硬化胆固醇可能参与了卡格列净的降糖疗效。依帕列净并非如此。（3）出乎意料的是，卡格列净导致体重减轻与其降糖疗效无关。
