Utsunomiya Kazunori, Kakiuchi Seigo, Senda Masayuki, Fujii Shoko, Kurihara Yuji, Gunji Ryoji, Koshida Ryusuke, Kameda Hiroyuki, Tamura Masahiro, Kaku Kohei
Center for Preventive Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Post Marketing Surveillance Department, Kowa Company, Ltd., Tokyo, Japan.
J Diabetes Investig. 2020 Jul;11(4):906-916. doi: 10.1111/jdi.13233. Epub 2020 Mar 15.
AIMS/INTRODUCTION: Tofogliflozin is a potent and highly selective sodium-glucose cotransporter 2 inhibitor, and is currently used to treat patients with type 2 diabetes mellitus. We designed a 3-year study of tofogliflozin in patients with type 2 diabetes mellitus to evaluate the safety and effectiveness in routine clinical practice. The 3- and 12-month interim analysis showed tofogliflozin was well-tolerated, safe and clinically effective. Here, we report the results of the 24-month interim analysis.
This is a 3-year prospective, observational and multicenter post-marketing study (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term).
Of the 6,897 patients enrolled, 6,712 and 6,461 patients were analyzed for the safety and effectiveness of tofogliflozin, respectively. During the 24-month observation period, the incidence rates of adverse drug reactions (ADRs) and serious adverse drug reactions were 11.25 and 1.21%, respectively. As to adverse drug reactions of special interest, the incidence rates of hypoglycemia, polyuria/pollakiuria, volume depletion-related events, urinary tract infections and genital infection were 0.83, 1.28, 1.46, 1.18 and 1.62%, respectively. Renal disorders, and cardiovascular and cerebrovascular disorders occurred in 0.63 and 0.76% of the patients, respectively. Glycated hemoglobin A1c and bodyweight decreased significantly by -0.70% (P < 0.0001) and -2.95 kg (P < 0.0001), respectively, from baseline to week 104 (last observation carried forward).
Significant safety concerns have not been observed, and clinical benefit including a long-term reduction in glycated hemoglobin A1c over a 104-week (24 months) observation period with weight loss was suggested in this 24-month interim analysis of the 3-year Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term in routine clinical practice.
目的/引言：托格列净是一种强效且高选择性的钠-葡萄糖协同转运蛋白2抑制剂，目前用于治疗2型糖尿病患者。我们设计了一项针对2型糖尿病患者使用托格列净的为期3年的研究，以评估其在常规临床实践中的安全性和有效性。3个月和12个月的中期分析表明，托格列净耐受性良好、安全且临床有效。在此，我们报告24个月中期分析的结果。
这是一项为期3年的前瞻性、观察性多中心上市后研究（日本托格列净治疗2型糖尿病患者/长期研究）。
在纳入的6897例患者中，分别对6712例和6461例患者进行了托格列净安全性和有效性分析。在24个月的观察期内，药物不良反应（ADR）和严重药物不良反应的发生率分别为11.25%和1.21%。至于特别关注的药物不良反应，低血糖、多尿/尿频、容量耗竭相关事件、尿路感染和生殖器感染的发生率分别为0.83%、1.28%、1.46%、1.18%和1.62%。肾脏疾病和心脑血管疾病的发生率分别为0.63%和0.76%。从基线到第104周（末次观察结转），糖化血红蛋白A1c和体重分别显著下降了-0.70%（P<0.0001）和-2.95 kg（P<0.0001）。
在这项为期3年的日本托格列净治疗2型糖尿病患者/长期研究的24个月中期分析中，在常规临床实践中未观察到重大安全问题，并提示在104周（24个月）观察期内具有临床益处，包括糖化血红蛋白A1c长期降低以及体重减轻。
