Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes: Pooled Analysis of Phase I-III Clinical Trials.
Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes: Pooled Analysis of Phase I-III Clinical Trials.
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DOI：
10.1007/s12325-017-0573-0
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发表时间：
2017-07
影响因子：
3.8
通讯作者：
Kaspers S
中科院分区：
文献类型：
--
作者：
Kohler S;Zeller C;Iliev H;Kaspers S
我们在临床试验中描述了恩格列净在2型糖尿病（T2 DM）患者中的安全性和耐受性，这些患者以1：1：1的比例随机接受安慰剂、恩格列净10 mg或恩格列净25 mg治疗。在15项随机化I-III期试验和4项扩展研究中分析了接受安慰剂（N = 4203）、恩格列净10 mg（N = 4221）或恩格列净25 mg（N = 4196）治疗的T2 DM患者的汇总数据。对至少服用一剂研究药物的参与者的不良事件（AE）进行描述性评估。计算每100患者-年的AE发生率，以校正试验间药物暴露的差异。安慰剂、恩格列净10 mg和25 mg组的总暴露量分别为7369、7782和7754患者-年。恩格列净治疗受试者中任何AE、重度AE、严重AE和导致停药的AE的发生率均不高于安慰剂治疗受试者。与安慰剂相比，恩格列净与低血糖风险增加无关，但接受背景磺酰脲类药物治疗的受试者除外。各治疗组与尿路感染一致的事件发生率相似（8.7-9.5/100患者-年）。恩格列净10 mg和25 mg治疗的受试者（分别为3.5和3.4/100患者-年）与安慰剂组（0.9/100患者-年）相比，生殖器感染相关事件的发生率更高。各治疗组与血容量不足一致的AE发生率相似（1.7-1.9/100患者-年），但在75岁或以上的受试者中，恩格列净10 mg和25 mg组高于安慰剂组（分别为3.2和3.0 vs. 2.3/100患者-年）。各治疗组的骨折、癌症事件、肾脏AE、静脉血栓栓塞事件、肝损伤、急性胰腺炎、下肢截肢和糖尿病酮症酸中毒的发生率相似。这项基于超过15，000患者-年暴露的汇总安全性数据分析支持恩格列净在T2 DM患者中的有利获益-风险特征。Boehringer Ingelheim Pharma GmbH.本文的在线版本（doi：10.1007/s12325-017-0573-0）包含补充材料，可供授权用户使用。
We characterized the safety and tolerability of empagliflozin in patients with type 2 diabetes (T2DM) randomized 1:1:1 to placebo, empagliflozin 10 mg, or empagliflozin 25 mg in clinical trials. Pooled data were analyzed from patients with T2DM treated with placebo (N = 4203), empagliflozin 10 mg (N = 4221), or empagliflozin 25 mg (N = 4196) in 15 randomized phase I–III trials plus four extension studies. Adverse events (AEs) were assessed descriptively in participants who took at least one dose of study drug. AE incidence rates per 100 patient-years were calculated to adjust for differences in drug exposure between trials. Total exposure was 7369, 7782, and 7754 patient-years in the placebo, empagliflozin 10 mg, and 25 mg groups, respectively. The incidence of any AEs, severe AEs, serious AEs, and AEs leading to discontinuation was no higher in participants treated with empagliflozin vs. placebo. Empagliflozin was not associated with an increased risk of hypoglycemia vs. placebo, except in participants on background sulfonylurea. The incidence of events consistent with urinary tract infection was similar across treatment groups (8.7–9.5/100 patient-years). Events consistent with genital infection occurred more frequently in participants treated with empagliflozin 10 and 25 mg (3.5 and 3.4/100 patient-years, respectively) than placebo (0.9/100 patient-years). The incidence of AEs consistent with volume depletion was similar across treatment groups (1.7–1.9/100 patient-years) but was higher with empagliflozin 10 mg and 25 mg vs. placebo in participants aged 75 years or older (3.2 and 3.0 vs. 2.3/100 patient-years, respectively). The rates of bone fractures, cancer events, renal AEs, venous thromboembolic events, hepatic injury, acute pancreatitis, lower limb amputations, and diabetic ketoacidosis were similar across treatment groups. This analysis of pooled safety data based on more than 15,000 patient-years’ exposure supports a favorable benefit–risk profile of empagliflozin in patients with T2DM. Boehringer Ingelheim Pharma GmbH. The online version of this article (doi:10.1007/s12325-017-0573-0) contains supplementary material, which is available to authorized users.
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影响因子：
9.3
作者：
Nishimura R;Tanaka Y;Koiwai K;Inoue K;Hach T;Salsali A;Lund SS;Broedl UC
通讯作者：
Broedl UC
影响因子：
3.5
作者：
Merker, L.;Haering, H-U.;Broedl, U. C.
通讯作者：
Broedl, U. C.
影响因子：
16.2
作者：
Rosenstock, Julio;Jelaska, Ante;Broedl, Uli C.
通讯作者：
Broedl, Uli C.
影响因子：
5.8
作者：
Ferrannini, E.;Seman, L.;Woerle, H. J.
通讯作者：
Woerle, H. J.
影响因子：
5.1
作者：
Haering, Hans-Ulrich;Merker, Ludwig;Broedl, Uli C.
通讯作者：
Broedl, Uli C.