Tobe Kazuyuki, Maegawa Hiroshi, Nakamura Ichiro, Uno Satoshi
First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194 Japan.
Department of Medicine, Shiga University of Medical Science, Shiga, Japan.
Diabetol Int. 2020 Nov 23;12(2):181-196. doi: 10.1007/s13340-020-00470-6. eCollection 2021 Apr.
STELLA-LONG TERM, a 3-year post-marketing surveillance study, evaluated the safety and effectiveness of the sodium-glucose cotransporter 2 inhibitor ipragliflozin in Japanese type 2 diabetes mellitus (T2DM) patients. Final results in the safety ( = 6697) and effectiveness populations ( = 5625) were analyzed by stratifying patients by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m) into four subgroups (≥ 90, 60 to < 90, 45 to < 60, and < 45) and two subgroups (≥ 60 and < 60). Adverse drug reaction (ADR) incidence, and changes from baseline in glycosylated hemoglobin (HbA1c), bodyweight, and eGFR were assessed. The percentage of patients experiencing ADRs and serious ADRs was similar across most eGFR subgroups. Polyuria/pollakiuria was the most common ADR. Renal disorders and volume depletion ADRs were more frequent in the subgroups with more severe renal impairment at baseline than in those with an eGFR of 60 to < 90 or ≥ 90 mL/min/1.73 m. Bodyweight and HbA1c decreased in all subgroups, the latter by - 0.91% to - 0.40% ( < 0.05 vs. baseline). eGFR increased in the 45 to < 60 mL/min/1.73 m subgroup (+ 1.42 ± 8.77 mL/min/1.73 m; = 0.006). It decreased in the ≥ 90 and 60 to < 90 mL/min/1.73 m subgroups (- 8.27 ± 13.73 and - 1.22 ± 10.34 mL/min/1.73 m; < 0.001), but not to < 60 mL/min/1.73 m. In conclusion, there were no new or unexpected safety findings in Japanese patients treated with ipragliflozin for T2DM, and long-term sustained improvements in HbA1c and bodyweight were observed regardless of the presence of renal impairment.
STELLA-LONG TERM是一项为期3年的上市后监测研究，评估了钠-葡萄糖协同转运蛋白2抑制剂依帕列净在日本2型糖尿病（T2DM）患者中的安全性和有效性。通过将患者按基线估计肾小球滤过率（eGFR，mL/min/1.73m²）分层为四个亚组（≥90、60至<90、45至<60和<45）和两个亚组（≥60和<60），对安全性人群（n = 6697）和有效性人群（n = 5625）的最终结果进行了分析。评估了药物不良反应（ADR）发生率以及糖化血红蛋白（HbA1c）、体重和eGFR相对于基线的变化。在大多数eGFR亚组中，发生ADR和严重ADR的患者百分比相似。多尿/尿频是最常见的ADR。与eGFR为60至<90或≥90 mL/min/1.73m²的亚组相比，基线时肾功能损害更严重的亚组中，肾脏疾病和容量耗竭性ADR更为常见。所有亚组的体重和HbA1c均下降，后者下降了-0.91%至-0.40%（与基线相比，P<0.05）。45至<60 mL/min/1.73m²亚组的eGFR升高（+1.42±8.77 mL/min/1.73m²；P = 0.006）。≥90和60至<90 mL/min/1.73m²亚组的eGFR下降（-8.27±13.73和-1.22±10.34 mL/min/1.73m²；P<0.001），但未降至<60 mL/min/1.73m²。总之，在接受依帕列净治疗T2DM的日本患者中未发现新的或意外的安全性发现，并且无论是否存在肾功能损害，均观察到HbA1c和体重的长期持续改善。
