Japan Association for Diabetes Education and Care, Tokyo, Japan.
Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan.
J Diabetes Investig. 2024 Nov;15(11):1585-1595. doi: 10.1111/jdi.14287. Epub 2024 Aug 14.
AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin.
This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss.
The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%-0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94-3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104.
Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.
目的/引言：钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂有效且安全地降低空腹和餐后高血糖，同时促进体重减轻。然而，其独特的作用机制引起了对其安全性的关注。因此，我们进行了一项大规模的、非商业化的、由研究者发起的关于 SGLT2 抑制剂托格列净的安全性和有效性的研究。
这是一项多中心、开放标签、非对照、前瞻性观察研究，在日本的医院和诊所进行，纳入了年龄≥20 岁、首次使用 SGLT2 抑制剂且已确诊 2 型糖尿病的患者。主要终点是特殊关注的药物不良反应（ADR）。次要终点包括所有其他 ADR 和不良事件、糖化血红蛋白（HbA1c）和体重减轻。
该研究于 2014 年 6 月至 2020 年 2 月进行，从 11480 名参与者中招募了 1103 家医疗机构的参与者；6967 名参与者完成了 104 周的随访。最常见的特殊关注的 ADR 是尿路感染和生殖道感染（1.53%），其次是容量耗竭（1.25%）。27 名参与者（0.24%）发生低血糖，1054 名参与者（9.18%）发生不良事件，645 名参与者（5.62%）发生 ADR。HbA1c 降低 0.85%（95%置信区间 0.82%-0.88%），体重减轻 3.05 公斤（95%置信区间 2.94-3.17 公斤）。在第 104 周时，51.70%的目标 HbA1c<7.0%、85.3%的目标 HbA1c<8.0%和 5.4%的目标 HbA1c<6.0%的参与者达到了 HbA1c 目标。
托格列净仅引起与 SGLT2 抑制剂特征相符的轻度或中度 ADR，无不可预测、新的、严重或高发生率的不良事件或 ADR。这项独立研究证实了托格列净在成年 2 型糖尿病患者中的安全性和有效性。
