Qiu Rong, Balis Dainius, Capuano George, Xie John, Meininger Gary
Janssen Research & Development, LLC, 920 Route 202 South, Raritan, NJ, 08869, USA.
Diabetes Ther. 2016 Dec;7(4):659-678. doi: 10.1007/s13300-016-0201-z. Epub 2016 Oct 12.
Metformin is typically the first pharmacologic treatment recommended for type 2 diabetes mellitus (T2DM), but many patients do not achieve glycemic control with metformin alone and eventually require combination therapy with other agents. Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was assessed in a comprehensive Phase 3 clinical development program consisting of ~10,000 participants, of which ~80% were on background therapy that consisted of metformin alone or in combination with other antihyperglycemic agents (AHAs; e.g., pioglitazone, sulfonylurea, and insulin). In addition, the efficacy and safety of canagliflozin and metformin as the initial combination therapy and canagliflozin monotherapy were assessed versus metformin in treatment-naïve patients with T2DM. Across studies in patients with T2DM who were on metformin alone or in combination with other AHAs, canagliflozin 100 and 300 mg provided improvements in glycated hemoglobin for up to 104 weeks. Canagliflozin was also associated with reductions in body weight and systolic blood pressure when added to background therapy consisting of metformin alone or with other AHAs. Canagliflozin was generally well tolerated, with increased incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition (i.e., genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs). Consistent with its insulin-independent mechanism of action, canagliflozin was associated with low rates of hypoglycemia when background therapy did not include sulfonylurea or insulin. Due to its favorable efficacy and safety profile, these results suggest that adding canagliflozin to a background regimen consisting of metformin or implementing treatment with a fixed-dose regimen of canagliflozin and metformin would provide an effective and safe treatment regimen for T2DM management.
Janssen Global Services, LLC.
二甲双胍通常是推荐用于2型糖尿病（T2DM）的首选药物治疗，但许多患者仅使用二甲双胍无法实现血糖控制，最终需要与其他药物联合治疗。卡格列净是一种钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，在一项由约10000名参与者组成的全面3期临床开发项目中进行了评估，其中约80%的参与者接受的背景治疗仅为二甲双胍或与其他降糖药（AHA；如吡格列酮、磺脲类和胰岛素）联合使用。此外，还评估了卡格列净与二甲双胍作为初始联合治疗以及卡格列净单药治疗在初治T2DM患者中的疗效和安全性，并与二甲双胍进行了对比。在单独使用二甲双胍或与其他AHA联合使用的T2DM患者的各项研究中，100毫克和300毫克的卡格列净可使糖化血红蛋白改善长达104周。当添加到仅含二甲双胍或与其他AHA的背景治疗中时，卡格列净还与体重减轻和收缩压降低有关。卡格列净总体耐受性良好，与SGLT2抑制机制相关的不良事件（AE）发生率增加（即生殖器真菌感染、尿路感染和渗透性利尿相关AE）。与其非胰岛素依赖的作用机制一致，当背景治疗不包括磺脲类或胰岛素时，卡格列净的低血糖发生率较低。由于其良好的疗效和安全性，这些结果表明，在由二甲双胍组成的背景治疗方案中添加卡格列净或采用卡格列净与二甲双胍的固定剂量方案进行治疗，将为T2DM管理提供一种有效且安全的治疗方案。
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