Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial.
Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial.
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达帕格列非佐以二甲双胍治疗二甲双胍控制不佳的 2 型糖尿病：一项为期 102 周的随机、双盲、安慰剂对照试验。
DOI：
10.1186/1741-7015-11-43
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发表时间：
2013-02-20
期刊：
影响因子：
9.3
通讯作者：
List JF
中科院分区：
文献类型：
--
作者：
Bailey CJ;Gross JL;Hennicken D;Iqbal N;Mansfield TA;List JF
用二甲双胍治疗2型糖尿病通常不能提供足够的血糖控制，因此有必要进行额外的治疗。在一项为期24周的临床试验中，研究中的钠葡萄糖共转运体2抑制剂达帕格列酮改善了用二甲双胍控制不佳的患者的血糖控制。本研究是对达帕利嗪在该人群中作为长期治疗方法进行评估的扩展。这是一项为期24周的3期多中心、随机、安慰剂对照、双盲、平行组试验的长期延长(共102周)。患者被随机分配(1：1：1：1)接受每日盲法治疗(安慰剂，或达帕利嗪2.5至5，或10毫克)加开放标签二甲双胍(≥，1,500毫克)。先前发表的主要终点是24周时糖化血红蛋白(HbA1c)较基线的变化。本文报告了102周的随访，在24周时进行协方差模型分析，最后一次观察继续进行；重复测量分析被用来评估与基线相比HbA1c、空腹血糖(FPG)和体重的变化。共有546名患者被随机分配到4种治疗方法中的1种。安慰剂组78周双盲延长期的完成率(63.5%)低于达帕格列酮组(68.3%至79.8%)。在第102周，安慰剂组较基线糖化血红蛋白(8.06%)的平均变化为+0.02%，而达格列酮2.5至5和10 mg组分别为-0.48%(P=0.0008)、-0.58%(P<；0.0001)和-0.78%(P<；0.0001)。此外，在102周时，所有达帕利氟津组的空腹血糖(-1.07至-1.47 mmol/L)和体重(-1.10至-1.74千克)较基线持续下降，而服用安慰剂的患者在这两个结果上均有上升。低血糖事件很少见，也不严重。有11.7%至14.6%的达格列酮患者和5.1%的安慰剂患者报告有生殖器感染的证据，其中一例与停药相关(达格列酮5毫克)。有证据表明有8.0%至13.3%的达帕利嗪患者和8.0%的安慰剂患者出现尿路感染，其中一例与停药有关(达帕利嗪2.5 mg)。在二甲双胍的基础上加用达帕格列酮102周，可以持续降低糖化血红蛋白、空腹血糖和体重，而不会增加仅用二甲双胍控制不佳的2型糖尿病患者发生低血糖的风险。ClinicalTrials.gov：NCT00528879
Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population. This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (≥1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight. A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5 to 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of placebo patients, with one related discontinuation (dapagliflozin 5 mg). Evidence suggestive of urinary tract infection was reported in 8.0% to 13.3% of dapagliflozin patients and 8.0% of placebo patients, with one related discontinuation (dapagliflozin 2.5 mg). Dapagliflozin added to metformin for 102 weeks enabled sustained reductions in HbA1c, FPG, and weight without increased risk of hypoglycemia in patients with type 2 diabetes who were inadequately controlled on metformin alone. ClinicalTrials.gov: NCT00528879
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影响因子：
168.9
作者：
Bailey, Clifford J.;Gross, Jorge L.;List, James F.
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