恩格列净单药治疗初治2型糖尿病患者的安全性、耐受性及对心血管代谢危险因素的影响：一项III期随机对照试验的双盲延长期试验
Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug-naïve patients with type 2 diabetes: a double-blind extension of a Phase III randomized controlled trial.
作者信息
Roden Michael, Merker Ludwig, Christiansen Anita Vedel, Roux Flavien, Salsali Afshin, Kim Gabriel, Stella Peter, Woerle Hans J, Broedl Uli C
机构信息
Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
出版信息
Cardiovasc Diabetol. 2015 Dec 23;14:154. doi: 10.1186/s12933-015-0314-0.
BACKGROUND
To investigate the long-term efficacy and safety of empagliflozin monotherapy compared with placebo and sitagliptin in drug-naïve patients with type 2 diabetes mellitus.
METHODS
Of 899 patients randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, placebo, or sitagliptin 100 mg once daily for 24 weeks, 615 continued in a double-blind extension trial for ≥52 weeks. Exploratory endpoints included changes from baseline in HbA1c, weight and blood pressure at week 76.
RESULTS
Compared with placebo, adjusted mean changes from baseline in HbA1c at week 76 were -0.78 % (95 % CI -0.94, -0.63; p < 0.001) and -0.89 % (95 % CI -1.04, -0.73; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight at week 76 were -1.8 kg (95 % CI -2.4, -1.3; p < 0.001) and -2.0 kg (95 % CI -2.6, -1.5; p < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to reductions in systolic blood pressure (SBP) compared with placebo in the primary analysis but not in sensitivity analyses. Compared with sitagliptin, empagliflozin 25 mg reduced HbA1c and both empagliflozin doses reduced weight and SBP. Adverse events (AEs) were reported in 76.8, 78.0, 76.4 and 72.2 % of patients on empagliflozin 10 mg, empagliflozin 25 mg, placebo and sitagliptin, respectively. Confirmed hypoglycaemic AEs (glucose ≤3.9 mmol/l and/or requiring assistance) were reported in two patients (0.9 %) per treatment group.
CONCLUSIONS
Empagliflozin monotherapy for ≥76 weeks was well tolerated and led to sustained reductions in HbA1c and weight compared with placebo.
TRIAL REGISTRATION
clinicaltrials.gov NCT01289990.
背景
在初治2型糖尿病患者中，比较恩格列净单药治疗与安慰剂和西格列汀的长期疗效和安全性。
方法
899例患者被随机分配，接受每日一次10mg恩格列净、25mg恩格列净、安慰剂或100mg西格列汀治疗24周，其中615例继续进行为期≥52周的双盲延长期试验。探索性终点包括第76周时糖化血红蛋白（HbA1c）、体重和血压相对于基线的变化。
结果
与安慰剂相比，第76周时，10mg恩格列净组和25mg恩格列净组HbA1c相对于基线的校正平均变化分别为-0.78%（95%置信区间-0.94，-0.63；p<0.001）和-0.89%（95%置信区间-1.04，-0.73；p<0.001）。与安慰剂相比，第76周时，10mg恩格列净组和25mg恩格列净组体重相对于基线的校正平均变化分别为-1.8kg（95%置信区间-2.4，-1.3；p<0.001）和-2.0kg（95%置信区间-2.6，-1.5；p<0.001）。在主要分析中，与安慰剂相比，恩格列净可降低收缩压（SBP），但在敏感性分析中未观察到。与西格列汀相比，25mg恩格列净可降低HbA1c，两种剂量的恩格列净均可降低体重和SBP。接受10mg恩格列净、25mg恩格列净、安慰剂和西格列汀治疗的患者中，不良事件（AE）的报告率分别为76.8%、78.0%、76.4%和72.2%。每个治疗组均有2例患者（0.9%）报告了确诊的低血糖不良事件（血糖≤3.9mmol/L和/或需要协助）。
结论
与安慰剂相比，恩格列净单药治疗≥76周耐受性良好，可使HbA1c和体重持续降低。
试验注册号
clinicaltrials.gov NCT01289990。
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