Pharmacovigilance Division, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
Japan Pharmacovigilance, MSD K.K., Tokyo, Japan.
Adv Ther. 2020 May;37(5):2442-2459. doi: 10.1007/s12325-020-01293-2. Epub 2020 Apr 18.
A post-marketing surveillance (PMS) study was conducted to confirm the long-term risk-benefit profile of sitagliptin administered to Japanese patients with type 2 diabetes mellitus (T2DM) under real-world conditions.
This prospective, multicentre, open-label PMS collected data from 3326 patients receiving sitagliptin according to the approved indication during the case registration period (July 2010-June 2012; observation period, 3 years). Safety was assessed via collection of data on adverse drug reactions (ADRs), estimated glomerular filtration rate (eGFR) and cardiovascular events whereas efficacy was assessed via changes in glycated hemoglobin (HbA1c).
In 3265 patients evaluated for safety, 270 ADRs occurred in 207 (6.3%) patients overall. Metabolism and nutrition disorders were the most common class of ADRs, occurring in 58 patients overall (53 non-serious, 5 serious) with hypoglycaemia (17 patients, 0.52%) the most common ADR. In patients with eGFR > 90 mL/min/1.73 m at baseline (mean ± SD, 106.42 ± 18.11 mL/min/1.73 m, n = 584), eGFR declined by 11.83 ± 17.53 mL/min/1.73 m (P < 0.0001; n = 360) over the observation period whereas eGFR appeared to be relatively maintained in patients with lower baseline eGFR levels. Cardiovascular events were infrequent [occurring in 4 of 84 (4.76%) patients at high cardiovascular risk] with no distinct features in this Japanese population and the cumulative incidence [8.42% (3.12-21.70) at 36 months; n = 32] was similar to that noted in previous studies involving sitagliptin. In patients evaluated for efficacy, the overall change in HbA1c from baseline to final evaluation was mean ± SD - 0.68 ± 1.34% (P < 0.0001, n = 2070). Reductions in HbA1c tended to be greater in younger patients and patients with higher body mass index (BMI) and HbA1c values at the start of administration.
Long-term sitagliptin administration in the routine clinical practice setting is associated with good efficacy, including as monotherapy, with no additional safety concerns.
本项上市后监测（PMS）研究旨在确认西格列汀在日本 2 型糖尿病（T2DM）患者中的长期风险-获益概况，研究在真实世界条件下开展。
该前瞻性、多中心、开放性 PMS 研究在病例登记期间（2010 年 7 月至 2012 年 6 月；观察期 3 年）共收集了 3326 例接受西格列汀治疗且符合适应证的患者数据。安全性评估通过药物不良反应（ADR）、估算肾小球滤过率（eGFR）和心血管事件的发生情况进行评估，疗效评估则通过糖化血红蛋白（HbA1c）的变化进行评估。
在 3265 例安全性评估患者中，207 例（6.3%）患者共发生 270 例 ADR。代谢和营养障碍是最常见的 ADR 类别，总体发生率为 58 例（53 例非严重，5 例严重），其中低血糖症（17 例，0.52%）是最常见的 ADR。在基线时 eGFR＞90mL/min/1.73m（平均值±标准差，106.42±18.11mL/min/1.73m，n=584）的患者中，eGFR 在观察期内下降了 11.83±17.53mL/min/1.73m（P＜0.0001；n=360），而 eGFR 水平较低的患者中，eGFR 似乎相对稳定。心血管事件较为少见[在 84 例（4.76%）高心血管风险患者中发生 4 例]，且在日本人群中无明显特征，36 个月时的累积发生率[8.42%（3.12-21.70）；n=32]与西格列汀既往研究中观察到的发生率相似。在疗效评估患者中，与基线相比，HbA1c 的总体变化为平均±标准差-0.68±1.34%（P＜0.0001，n=2070）。在年轻患者和起始治疗时 HbA1c 值和体重指数（BMI）较高的患者中，HbA1c 的降低幅度更大。
西格列汀在常规临床实践环境中的长期应用与良好的疗效相关，包括单药治疗，且无额外的安全性问题。
