Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan.
Diabetes Obes Metab. 2018 Apr;20(4):812-820. doi: 10.1111/dom.13152. Epub 2017 Dec 5.
The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin.
The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values.
The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were -1.09% ± 0.85% and -0.88% ± 0.86% for HbA1c, -1.40% ± 2.54% and -2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period.
This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients.
本研究旨在评估卡格列净作为附加疗法用于血糖控制不佳的日本 2 型糖尿病患者的长期疗效和安全性，这些患者正在接受胰岛素治疗。
研究包括 16 周的双盲期，在此期间，患者被随机分配至安慰剂（P；N=70）或卡格列净（100mg，CAN；N=76）组，随后进入 36 周的开放标签期，所有患者均接受卡格列净治疗。疗效终点包括从基线到治疗结束时 HbA1c 的变化。安全性终点为不良事件、低血糖事件和实验室检查值。
从基线（末次观测值结转）的变化（均值±标准差），P/CAN 和 CAN/CAN 组分别为 -1.09%±0.85%和-0.88%±0.86%的 HbA1c，-1.40%±2.54%和-2.14%±2.75%的体重，以及 7.84%±14.37%和 8.91%±10.80%的 HOMA2-%B（均 P<.001）。P/CAN 组和 CAN/CAN 组分别有 85.1%和 92.0%的患者发生不良事件。低血糖事件分别为 43.3%和 54.7%。所有低血糖事件均为轻度，减少胰岛素剂量可降低低血糖事件的发生率。事后有序逻辑回归模型/逻辑回归模型显示，在双盲期和卡格列净全治疗期，0 周时血清 C 肽较低是 P 组和 CAN 组发生低血糖的危险因素。
本研究表明卡格列净联合胰岛素治疗可长期有效且安全地用于日本 2 型糖尿病患者。
