Department of Pharmacy, Peking University Third Hospital, Beijing, China.
PLoS One. 2018 May 22;13(5):e0197321. doi: 10.1371/journal.pone.0197321. eCollection 2018.
To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D).
A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs). Dichotomous data were presented as Mantel-Haenzel risk ratios (RRs).
Thirty-nine references of 30 RCTs involving 29,938 patients were analyzed. Compared with placebo, saxagliptin significantly reduced glycated hemoglobin (HbA1c, WMD -0.52%, 95% CI -0.60 to -0.44) and fasting plasma glucose (WMD -13.78 mg/dL, 95% CI -15.31 to -12.25), and increased the proportion of patients achieving HbA1c <7% (RR 1.64, 95% CI 1.53 to 1.75). When combined with submaximal-dose metformin, saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose (RR 2.38, 95% CI 1.17 to 4.83) and uptitrated metformin (RR 1.30, 95% CI 1.04 to 1.63). Saxagliptin was similar to other DPP-4 inhibitors but inferior to liraglutide and dapagliflozin on glycemic control. Saxagliptin significantly decreased the incidences of overall adverse events compared with acarbose (RR 0.71, 95% CI 0.57 to 0.89) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71) when added to metformin. Weight gain and hypoglycemia with saxagliptin was slightly but significantly higher than placebo and lower than sulfonylureas. Saxagliptin did not increase the risk of arthralgia, heart failure, pancreatitis and other adverse events.
Generally, saxagliptin has similar efficacy compared with most oral antidiabetic drugs and may be more effective than acarbose, while having a better safety profile than both acarbose and sulfonylureas.
评估沙格列汀治疗 2 型糖尿病（T2D）的疗效和安全性。
系统检索 PubMed、Embase、Cochrane 图书馆、Web of Science、ClinicalTrials.gov 及两个中文数据库，查找比较沙格列汀与安慰剂或阳性对照药物治疗 T2D 的随机对照试验（RCT）。检索截止日期为 2017 年 7 月，同时进行补充检索以获取截至 2018 年 3 月的文献。对连续性数据，采用逆方差法进行合并，计算加权均数差（WMD）；二分类数据采用 Mantel-Haenzel 风险比（RR）表示。
共纳入 30 项 RCT 的 39 篇文献，涉及 29938 例患者。与安慰剂相比，沙格列汀可显著降低糖化血红蛋白（HbA1c，WMD-0.52%，95%CI-0.60 至-0.44）和空腹血糖（WMD-13.78mg/dL，95%CI-15.31 至-12.25），并增加 HbA1c＜7%患者的比例（RR 1.64，95%CI 1.53 至 1.75）。与阿卡波糖相比，当与亚最大剂量二甲双胍联合使用时，沙格列汀可显著增加 HbA1c＜7%患者的比例（RR 2.38，95%CI 1.17 至 4.83）；与二甲双胍加量相比，可增加 HbA1c＜7%患者的比例（RR 1.30，95%CI 1.04 至 1.63）。沙格列汀在血糖控制方面与其他二肽基肽酶-4 抑制剂相似，但不如利拉鲁肽和达格列净。与阿卡波糖（RR 0.71，95%CI 0.57 至 0.89）和利拉鲁肽（RR 0.41，95%CI 0.24 至 0.71）相比，沙格列汀联合二甲双胍可降低总体不良事件的发生率。与安慰剂和磺酰脲类药物相比，沙格列汀引起的体重增加和低血糖发生率虽略有升高但具有统计学意义，且低于磺酰脲类药物。沙格列汀不会增加关节痛、心力衰竭、胰腺炎等不良反应的发生风险。
总体而言，沙格列汀与大多数口服降糖药疗效相当，可能优于阿卡波糖，且安全性优于阿卡波糖和磺酰脲类药物。
