Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA.
Diabet Med. 2013 Dec;30(12):1472-6. doi: 10.1111/dme.12267. Epub 2013 Jul 19.
To evaluate the safety of saxagliptin ± metformin over 4 years in patients with Type 2 diabetes mellitus.
Drug-naive (n = 401; study 11) or metformin-treated (n = 743; study 14) adults with HbA(1c) of 53-86 mmol/mol (7.0-10%) were enrolled in two randomized, placebo-controlled, double-blind trials of saxagliptin 2.5, 5 or 10 mg/day. Patients rescued during or completing 24 weeks of treatment could continue in a 42-month long-term blinded phase, for which the primary goal was assessment of safety and tolerability. Between-group efficacy was not evaluated in the long-term phase of study 11. Time to rescue or discontinuation because of inadequate glycaemic control, change from baseline in HbA(1c) and percentages of patients achieving HbA(1c) < 53 mmol/mol (< 7.0%) were assessed in study 14.
No new safety findings were noted during the long-term phase. Most adverse events were mild or moderate, with slightly greater frequency of upper respiratory infections with saxagliptin. Hypoglycaemic event rates were similar with saxagliptin and placebo. In study 14, time to rescue or discontinuation because of inadequate glycaemic control was longer with saxagliptin plus metformin than for placebo plus metformin. From baseline to week 154, HbA(1c) decreased with saxagliptin but increased with placebo.
Saxagliptin monotherapy or add-on to metformin is generally safe and well tolerated, with no increased risk of hypoglycaemia, for up to 4 years.
评估 2 型糖尿病患者使用沙格列汀 ± 二甲双胍治疗 4 年的安全性。
本研究纳入了两项随机、安慰剂对照、双盲试验，共纳入了初治（n = 401；研究 11）或二甲双胍治疗（n = 743；研究 14）、糖化血红蛋白（HbA1c）为 53-86mmol/mol（7.0-10%）的成年患者。患者在治疗 24 周期间或结束后可继续接受为期 42 个月的长期盲法治疗，主要目的是评估安全性和耐受性。在研究 11 的长期阶段，未评估组间疗效。评估因血糖控制不佳而进行抢救或停药的时间、与基线相比 HbA1c 的变化以及达到 HbA1c＜53mmol/mol（＜7.0%）的患者比例。
长期治疗阶段未发现新的安全性问题。大多数不良事件为轻度或中度，沙格列汀组上呼吸道感染的频率略高。沙格列汀与安慰剂组的低血糖事件发生率相似。在研究 14 中，因血糖控制不佳而进行抢救或停药的时间，沙格列汀联合二甲双胍组长于安慰剂联合二甲双胍组。从基线到第 154 周，沙格列汀可降低 HbA1c，但安慰剂可升高 HbA1c。
沙格列汀单药治疗或与二甲双胍联合使用，安全性良好，耐受性良好，4 年内低血糖风险无增加。
