Boehringer Ingelheim International GmbH, Ingelheim, Germany.
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Adv Ther. 2020 Aug;37(8):3463-3484. doi: 10.1007/s12325-020-01329-7. Epub 2020 May 5.
The aim of this analysis was to characterize the safety and tolerability of empagliflozin in patients with type 2 diabetes mellitus (T2DM) who were randomized to empagliflozin (10/25 mg) or placebo in clinical trials.
Pooled data from 20 trials were analyzed for patients with T2DM treated with empagliflozin 10 mg (n = 4858), empagliflozin 25 mg (n = 5057), or placebo (n = 4904). The dataset comprised 15 randomized phase I-III trials, an extension trial and dose escalation studies. Adverse events (AEs) were assessed descriptively in participants who took ≥ 1 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 16,480 and 7857 patient-years in the pooled empagliflozin 10/25 mg and placebo groups, respectively. The incidence of any AEs, AEs leading to treatment discontinuation, severe AEs, and serious AEs was similar across groups. The frequency of serious AEs requiring hospitalization was 18.6% for the empagliflozin 10/25 mg group and 21.3% for the placebo group. The empagliflozin 10/25 mg group was not associated with a higher rate of confirmed hypoglycemia versus placebo, except in patients co-administered insulin and/or a sulfonylurea (31.5% vs. 30.2%, respectively). The incidence of events consistent with urinary tract infections (UTI) was also similar for the empagliflozin 10/25 mg group versus placebo (9.27 vs. 9.70/100 patient-years, respectively). History of UTI was identified as a risk factor for UTI during treatment. Events consistent with genital infections occurred more frequently with empagliflozin 10/25 mg than placebo (3.54 vs. 0.95/100 patient-years, respectively). The frequency of AEs consistent with volume depletion was similar across groups, but higher with empagliflozin 10/25 mg than placebo in patients aged 75 to < 85 years and those on loop diuretics at baseline.
This comprehensive analysis confirms that both empagliflozin 10 mg and 25 mg are well tolerated in patients with T2DM, reinforcing the established clinical safety profile of empagliflozin.
本分析旨在描述在临床试验中接受恩格列净治疗的 2 型糖尿病（T2DM）患者的安全性和耐受性，这些患者被随机分配至恩格列净（10/25mg）或安慰剂组。
对接受恩格列净 10mg（n=4858）、25mg（n=5057）或安慰剂（n=4904）治疗的 T2DM 患者的 20 项临床试验汇总数据进行分析。数据集包括 15 项随机 I-III 期试验、一项扩展试验和剂量递增研究。描述性评估了至少接受一剂研究药物的参与者的不良事件（AE）。根据试验间药物暴露的差异，计算了每 100 患者-年的 AE 发生率。
在恩格列净 10/25mg 与安慰剂组的汇总人群中，总暴露分别为 16480 和 7857 患者-年。各组之间任何 AE、导致治疗中止的 AE、严重 AE 和严重不良事件（SAE）的发生率相似。需要住院治疗的严重 AE 频率为恩格列净 10/25mg 组 18.6%，安慰剂组 21.3%。与安慰剂相比，恩格列净 10/25mg 组低血糖症的确诊率没有更高，除了与胰岛素和/或磺酰脲类药物联合治疗的患者（分别为 31.5%和 30.2%）。与尿路感染（UTI）一致的事件发生率在恩格列净 10/25mg 组与安慰剂组之间也相似（分别为 9.27 和 9.70/100 患者-年）。UTI 病史被确定为治疗期间 UTI 的一个风险因素。生殖系统感染一致的事件发生率恩格列净 10/25mg 组高于安慰剂组（分别为 3.54 和 0.95/100 患者-年）。各组容量耗竭相关不良事件的频率相似，但在年龄 75 岁至<85 岁的患者和基线时使用袢利尿剂的患者中，恩格列净 10/25mg 组高于安慰剂组。
这项全面分析证实，恩格列净 10mg 和 25mg 在 T2DM 患者中均具有良好的耐受性，强化了恩格列净已确立的临床安全性特征。
