Keenan Research Centre, The Li Ka Shing Knowledge Institute, St. Michael's Hospital; Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada
Department of Endocrinology & Metabolism, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Diabetes Care. 2015 Mar;38(3):355-64. doi: 10.2337/dc13-2762. Epub 2014 Sep 9.
To assess the efficacy/safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with glimepiride over 104 weeks in patients with type 2 diabetes inadequately controlled with metformin.
In this randomized, double-blind study, patients (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride (titrated up to 6 or 8 mg/day) during a 52-week core period followed by a 52-week extension.
At week 104, reductions from baseline in A1C were -0.65%, -0.74%, and -0.55% (-7.1, -8.1, and -6.0 mmol/mol) with canagliflozin 100 and 300 mg and glimepiride, respectively. Durability analyses showed sustained A1C lowering with both canagliflozin doses versus glimepiride. Reductions in body weight (-4.1%, -4.2%, and 0.9%, respectively) and systolic blood pressure (-2.0, -3.1, and 1.7 mmHg, respectively) were seen with canagliflozin 100 and 300 mg compared with glimepiride at week 104. The overall adverse event (AE) incidence was 73.3%, 77.9%, and 78.4% with canagliflozin 100 and 300 mg and glimepiride; the incidence of AE-related discontinuations was low across groups (6.2%, 9.5%, and 7.3%, respectively). Incidences of genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs were higher with canagliflozin than glimepiride; these were generally mild to moderate in intensity and led to few discontinuations. Fewer patients had hypoglycemia episodes with canagliflozin 100 and 300 mg than glimepiride (6.8%, 8.2%, and 40.9%). Mild decreases in estimated glomerular filtration rate occurred initially with canagliflozin; these attenuated over 104 weeks.
Canagliflozin provided durable glycemic improvements compared with glimepiride and was generally well tolerated in patients with type 2 diabetes receiving background treatment with metformin over 104 weeks.
评估钠-葡萄糖协同转运蛋白 2 抑制剂卡格列净在二甲双胍控制不佳的 2 型糖尿病患者中的疗效/安全性，与格列美脲相比，疗程为 104 周。
在这项随机、双盲研究中，患者（N=1450）在 52 周的核心期内接受卡格列净 100 或 300mg 或格列美脲（滴定至 6 或 8mg/天）治疗，随后进行 52 周的扩展期。
在第 104 周时，与格列美脲相比，卡格列净 100mg 和 300mg 组的糖化血红蛋白（HbA1c）自基线的降幅分别为-0.65%、-0.74%和-0.55%（-7.1、-8.1 和-6.0mmol/mol）。耐久性分析显示，与格列美脲相比，两种剂量的卡格列净均可持续降低 HbA1c。与格列美脲相比，卡格列净 100mg 和 300mg 组的体重（分别为-4.1%、-4.2%和 0.9%）和收缩压（分别为-2.0mmHg、-3.1mmHg 和 1.7mmHg）也有所降低。第 104 周时，卡格列净 100mg 和 300mg 组的总体不良事件（AE）发生率分别为 73.3%、77.9%和 78.4%，AE 相关停药率较低（分别为 6.2%、9.5%和 7.3%）。与格列美脲相比，卡格列净组的生殖器真菌感染、尿路感染和渗透性利尿相关 AE 的发生率更高；这些不良反应通常为轻度至中度，导致停药的情况很少。卡格列净 100mg 和 300mg 组低血糖发作的患者少于格列美脲组（6.8%、8.2%和 40.9%）。卡格列净治疗最初会导致估算肾小球滤过率（eGFR）轻度下降，104 周后逐渐减轻。
与格列美脲相比，卡格列净可提供持久的血糖改善，并且在接受二甲双胍背景治疗的 2 型糖尿病患者中耐受性良好。
