Center for Preventive Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Medical Affairs, Sanofi K.K., Tokyo, Japan.
J Diabetes Investig. 2021 Feb;12(2):184-199. doi: 10.1111/jdi.13333. Epub 2020 Aug 25.
AIMS/INTRODUCTION: Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers plasma glucose levels by enhancing urinary glucose excretion. After its approval in Japan in 2014 for the treatment of type 2 diabetes mellitus, we carried out a 3-year prospective observational post-marketing surveillance study in Japanese patients (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term [J-STEP/LT]).
This surveillance was carried out between September 2014 and February 2019, and recorded safety in terms of adverse drug reactions (ADRs) and ADRs of special interest, and effectiveness in terms of changes in glycated hemoglobin and bodyweight from baseline to last observation carried forward.
Of 6,897 patients with type 2 diabetes mellitus registered, 6,711 and 6,451 were analyzed for safety and effectiveness, respectively. ADRs were reported in 846 patients (12.61%), with serious ADRs in 101 patients (1.5%). ADRs of special interest included hypoglycemia (62 patients [0.9%]), polyuria/pollakiuria (90 [1.3%]), volume depletion-related disorders (135 [2.0%]), urinary tract infections (91 [1.4%]), genital infections (117 [1.7%]) and skin diseases (53 [0.8%]). One case of diabetic ketoacidosis was reported. The mean ± standard deviation changes from baseline to last observation carried forward in glycated hemoglobin and bodyweight were -0.68 ± 1.34% (n = 6,158, P < 0.0001) and -3.13 ± 4.67 kg (n = 5,213, P < 0.0001), respectively.
J-STEP/LT, a 3-year, prospective, observational, post-marketing study in Japan, found no unprecedented ADRs, and consistent reductions from baseline in glycated hemoglobin and bodyweight over the observation period. The present results provide further evidence regarding the safety and tolerability of tofogliflozin in Japanese patients with type 2 diabetes mellitus.
目的/引言：托格列净是一种钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂，通过增强尿糖排泄降低血糖水平。2014 年在日本批准用于 2 型糖尿病治疗后，我们在日本 2 型糖尿病患者中开展了一项为期 3 年的前瞻性观察性上市后监测研究（日本托格列净治疗 2 型糖尿病患者/长期研究[J-STEP/LT]）。
该监测于 2014 年 9 月至 2019 年 2 月进行，记录安全性方面的药物不良反应（ADR）和特殊关注的 ADR，以及有效性方面的糖化血红蛋白和体重从基线到最后一次向前结转观察的变化。
在登记的 6897 例 2 型糖尿病患者中，分别有 6711 例和 6451 例患者进行了安全性和有效性分析。846 例（12.61%）患者报告了 ADR，101 例（1.5%）患者报告了严重 ADR。特殊关注的 ADR 包括低血糖（62 例[0.9%]）、多尿/尿频（90 例[1.3%]）、容量消耗相关疾病（135 例[2.0%]）、尿路感染（91 例[1.4%]）、生殖器感染（117 例[1.7%]）和皮肤病（53 例[0.8%]）。报告了 1 例糖尿病酮症酸中毒。从基线到最后一次向前结转观察的糖化血红蛋白和体重的平均变化分别为-0.68±1.34%（n=6158，P<0.0001）和-3.13±4.67kg（n=5213，P<0.0001）。
J-STEP/LT 是一项在日本开展的为期 3 年的前瞻性观察性上市后监测研究，未发现新的 ADR，并且在整个观察期间，糖化血红蛋白和体重均从基线水平持续降低。本研究结果进一步证明了托格列净在日本 2 型糖尿病患者中的安全性和耐受性。
