Long-term safety and efficacy of imeglimin in Japanese individuals with type 2 diabetes and chronic kidney disease: A 52-week postmarketing clinical study (TWINKLE)

IF 3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Tetsuya Babazono, Takeshi Osonoi, Hideki Okamoto, Yukiko Onishi, Shinya Nakamoto, Masayuki Kashima, Daiji Kawanami, Eitaro Nakashima, Kei Watabe, Noriko Nunami, Katsuhiko Hagi
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Abstract

Aim

To evaluate the long-term safety and efficacy of imeglimin in Japanese individuals with type 2 diabetes (T2D) and advanced chronic kidney disease (CKD).

Materials and Methods

This open-label, single-arm, multicenter, phase 4 study (TWINKLE) enrolled individuals with T2D and estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2, treated with ≤1 oral hypoglycemic agent. Participants received 500 mg of imeglimin twice daily if eGFR was 15 to <45 mL/min/1.73 m2 or 500 mg once daily if eGFR was <15 mL/min/1.73 m2, as monotherapy or in combination with their existing hypoglycemic agent, for 52 weeks. Dose adjustments were permitted based on safety and eGFR.

Results

Among 60 participants (CKD stages: G3b: n = 42; G4: n = 16; G5: n = 2), adverse events (AEs) occurred in 41 participants (68.3%), with no increased incidence across CKD stages. The most common AE was diarrhea (n = 6, 10.0%). Baseline mean (SD) HbA1c, glycated albumin (GA), and fasting plasma glucose (FPG) levels were 7.59% (0.68%), 22.53% (3.27%), and 151.8 (28.86) mg/dL, respectively. At week 24, mean (SD) changes from baseline were −0.53% (0.51%) for HbA1c, −2.37% (2.08%) for GA, and −13.6 (20.87) mg/dL for FPG. At week 52 (last observation carried forward [LOCF]), mean changes were −0.26% (0.88%), −1.59% (3.04%), and −7.0 (31.17) mg/dL. The proportion achieving HbA1c < 7.0% increased from 13.3% at baseline to 50.0% at week 52 (LOCF).

Conclusions

This study confirmed the favorable safety profile and sustained glycemic efficacy of imeglimin in Japanese individuals with T2D and CKD stages G3b–5, supporting its use with dose adjustment in this population.

Abstract Image

伊米明在日本2型糖尿病和慢性肾脏疾病患者中的长期安全性和有效性:一项52周的上市后临床研究(TWINKLE)
目的:评价伊米明在日本2型糖尿病(T2D)和晚期慢性肾脏疾病(CKD)患者中的长期安全性和有效性。材料和方法:这项开放标签、单组、多中心、4期研究(TWINKLE)招募了T2D患者,估计肾小球滤过率(eGFR) 2,接受≤1种口服降糖药治疗。如果eGFR为15 - 2,受试者接受500mg伊米明,每日2次;如果eGFR为2,受试者接受500mg,每日1次,作为单药治疗或与现有降糖药联合治疗,疗程52周。允许根据安全性和eGFR调整剂量。结果:60名参与者(CKD分期:G3b: n = 42;G4: n = 16;G5: n = 2), 41名参与者(68.3%)发生了不良事件(ae),在CKD分期中发生率没有增加。最常见的AE是腹泻(n = 6, 10.0%)。基线平均(SD) HbA1c、糖化白蛋白(GA)和空腹血糖(FPG)水平分别为7.59%(0.68%)、22.53%(3.27%)和151.8 (28.86)mg/dL。在第24周,与基线相比,HbA1c的平均(SD)变化为-0.53% (0.51%),GA为-2.37% (2.08%),FPG为-13.6 (20.87)mg/dL。第52周(最后一次观察结转[LOCF]),平均变化分别为-0.26%(0.88%)、-1.59%(3.04%)和-7.0 (31.17)mg/dL。结论:本研究证实伊米明在日本T2D和CKD G3b-5期患者中具有良好的安全性和持续的降糖疗效,支持在该人群中调整剂量使用。
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来源期刊
Journal of Diabetes Investigation
Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
9.40%
发文量
218
审稿时长
6-12 weeks
期刊介绍: Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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