Diabetes Care：Canagliflozin降糖效果不劣于西格列汀

　　对于二甲双胍联合磺脲类药物血糖控制不佳的2型糖尿病患者，canagliflozin [一种钠—葡萄糖协同转运子2（SGLT2）抑制剂] 或可成为糖尿病治疗的又一选择。在一项3期临床试验中canagliflozin显示出降糖与体重改善方面相对于西格列汀的优势，但研究同时指出服用canagliflozin的女性患者需注意生殖器真菌感染风险。该研究2013年4月5日发表在《糖尿病护理》杂志。

　　这项为期52周的随机双盲研究入选755例接受二甲双胍于磺脲类药物联合治疗的2型糖尿病患者，每日分别给予患者服用canagliflozin 300mg 或西格列汀100 mg，主要终点为基线至52周时糖化血红蛋白水平的变化。次级终点包括空腹血糖（FPG）、收缩压（BP）变化，以及体重改变、甘油三酯和高密度脂蛋白胆固醇的改变程度。

　　结果显示第52周时canagliflozin组疗效不劣于西格列汀组，后续分析显示降糖效果甚至优于前者[HbA1c分别降低−1.03%（−11.3 mmol/mol）和−0.66% （−7.2 mmol/mol）]。最小二乘法分析两组差异−0.37%或−4.0 mmol/mol。Canagliflozin组患者FPG、体重及BP下降更显著（P<0.001）。总体不良事件发生率两组相似，严重不良事件和因不良事件停药比例极低。

　　在安全性方面，生殖器真菌感染及渗透性利尿相关不良事件在两组患者均有发生，1例患者退出试验。两组低血糖事件发生率相似。

与糖尿病相关的拓展阅读：

• Hypertension：无糖尿病患者ACEI与小剂量噻嗪利尿剂联用对胰岛素作用影响不大
• Nat Rev Cardiol：戒烟降低非糖尿病患者心血管疾病风险
• Diabetes Care：NT-proBNP为老年糖尿病患者短期死亡强预测因子
• MD Consult：Invokana获准用于2型糖尿病
• Eur J Endocrinol:抑郁与1型糖尿病血糖控制不佳相关
• Eur J Med Res：糖尿病患者需要口腔健康教育
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Canagliflozin Compared With Sitagliptin for Patients With Type 2 Diabetes Who Do Not Have Adequate Glycemic Control With Metformin Plus Sulfonylurea
A 52-week randomized trial
OBJECTIVE
To evaluate the efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 inhibitor, compared with sitagliptin in subjects with type 2 diabetes inadequately controlled with metformin plus sulfonylurea.
RESEARCH DESIGN AND METHODS
In this 52-week, randomized, double-blind, active-controlled, phase 3 study, subjects using stable metformin plus sulfonylurea (N = 755) received canagliflozin 300 mg or sitagliptin 100 mg daily. Primary end point was change from baseline in A1C at 52 weeks. Secondary end points included change in fasting plasma glucose (FPG) and systolic blood pressure (BP), and percent change in body weight, triglycerides, and HDL cholesterol. Safety was assessed based on adverse event (AE) reports.
RESULTS
At 52 weeks, canagliflozin 300 mg demonstrated noninferiority and, in a subsequent assessment, showed superiority to sitagliptin 100 mg in reducing A1C (−1.03% [−11.3 mmol/mol] and −0.66% [−7.2 mmol/mol], respectively; least squares mean difference between groups, −0.37% [95% CI, −0.50 to −0.25] or −4.0 mmol/mol [−5.5 to −2.7]). Greater reductions in FPG, body weight, and systolic BP were observed with canagliflozin versus sitagliptin (P < 0.001). Overall AE rates were similar with canagliflozin (76.7%) and sitagliptin (77.5%); incidence of serious AEs and AE-related discontinuations was low for both groups. Higher incidences of genital mycotic infections and osmotic diuresis–related AEs were observed with canagliflozin, which led to one discontinuation. Hypoglycemia rates were similar in both groups.
CONCLUSION
Findings suggest that canagliflozin may be a new therapeutic tool providing better improvement in glycemic control and body weight reduction than sitagliptin, but with increased genital infections in subjects with type 2 diabetes using metformin plus sulfonylurea.