Diabetes-Zentrum, Quakenbrück Hospital, Quakenbrück, Germany.
Aggarwal and Associates, Ltd, Brampton, Ontario, Canada.
Diabetes Obes Metab. 2016 Nov;18(11):1128-1133. doi: 10.1111/dom.12741. Epub 2016 Aug 19.
Greater reductions in glycated haemoglobin (HbA1c) with saxagliptin, a dipeptidyl peptidase-4 inhibitor, versus placebo add-on in patients with type 2 diabetes who had inadequate glycaemic control with dapagliflozin 10 mg/d plus metformin were demonstrated after 24 weeks of treatment. Results over 52 weeks of treatment were assessed in this analysis.
Patients (mean baseline HbA1c 7.9%) receiving open-label dapagliflozin 10 mg/d plus metformin were randomized to double-blind saxagliptin 5 mg/d or placebo add-on.
The adjusted mean change from baseline to week 52 in HbA1c was greater with saxagliptin than with placebo add-on -0.38% vs 0.05%; difference -0.42% (95% confidence interval -0.64, -0.20)]. More patients achieved the HbA1c target of <7% with saxagliptin than with placebo add-on (29% vs 13%), and fewer patients were rescued or discontinued the study for lack of glycaemic control with saxagliptin than with placebo add-on (19% vs 28%). Reductions from baseline in body weight (≤1.5 kg) occurred in both groups. Similar proportions of patients reported ≥1 adverse event with saxagliptin (58.2%) and placebo add-on (58.0%); no new safety signals were detected. Hypoglycaemia was infrequent in both treatment groups (≤2.5%), with no major episodes. The rate of urinary tract infections was similar in the saxagliptin and placebo add-on groups (7.8% vs 7.4%). The incidence of genital infections was 3.3% with saxagliptin versus 6.2% with placebo add-on.
Triple therapy with saxagliptin add-on to dapagliflozin plus metformin for 52 weeks resulted in sustained improvements in glycaemic control without an increase in body weight or increased risk of hypoglycaemia.
在接受达格列净 10mg/d 加二甲双胍治疗但血糖控制仍不理想的 2 型糖尿病患者中，与安慰剂加用相比，二肽基肽酶-4 抑制剂沙格列汀可使糖化血红蛋白（HbA1c）进一步降低，这在 24 周的治疗中得到了证实。本分析评估了治疗 52 周的结果。
接受达格列净 10mg/d 加二甲双胍开放标签治疗的患者（平均基线 HbA1c 为 7.9%）被随机分配接受双盲沙格列汀 5mg/d 或安慰剂加用。
与安慰剂加用相比，沙格列汀治疗 52 周时 HbA1c 从基线的平均变化更大，为-0.38%，而安慰剂加用为 0.05%；差值为-0.42%（95%置信区间为-0.64，-0.20]）。与安慰剂加用相比，更多的患者达到了 HbA1c<7%的目标（29%比 13%），而由于血糖控制不佳而需要抢救或退出研究的患者则更少（19%比 28%）。两组患者体重（≤1.5kg）均有下降。沙格列汀组（58.2%）和安慰剂加用组（58.0%）报告≥1 例不良事件的比例相似；未发现新的安全信号。两组低血糖的发生频率均较低（≤2.5%），且无重大事件发生。尿路感染的发生率在沙格列汀组和安慰剂加用组相似（7.8%比 7.4%）。沙格列汀组生殖道感染的发生率为 3.3%，安慰剂加用组为 6.2%。
在达格列净加二甲双胍治疗的基础上加用沙格列汀治疗 52 周，可持续改善血糖控制，而不会导致体重增加或增加低血糖风险。
