Safety and Effectiveness of Ipragliflozin for Type 2 Diabetes in Japan: 12-Month Interim Results of the STELLA-LONG TERM Post-Marketing Surveillance Study

Ichiro Nakamura, Hiroshi Maegawa, Kazuyuki Tobe, Satoshi Uno, Ichiro Nakamura, Hiroshi Maegawa, Kazuyuki Tobe, Satoshi Uno

Abstract

Introduction: The present interim report of the STELLA-LONG TERM study aimed to examine the safety and effectiveness of ipragliflozin in real-word clinical practice in Japan using data up to 12 months. We also evaluated the effect of ipragliflozin on aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with normal vs. abnormal liver function.

Methods: This is an ongoing 3-year post-marketing surveillance study. We analyzed data from Japanese type 2 diabetes mellitus (T2DM) patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan, and whose data were locked by 16 January 2018. The incidence of adverse drug reactions (ADRs) was evaluated for safety. Changes in glycemic control and body weight were evaluated for effectiveness. The effect on liver function was evaluated by changes in the fatty liver index, and changes in AST and ALT were evaluated in patients with normal and abnormal liver function.

Results: The safety analysis set comprised 11,051 patients and the efficacy analysis set comprised 8788 patients. The incidence rates of ADRs and serious ADRs were 14.6% (1616/11,051) and 0.97% (107/11,051), respectively. Significant reductions (all P < 0.001 vs. baseline, paired t test) in glycated hemoglobin (- 0.8%), fasting plasma glucose (- 31.9 mg/dL), body weight (- 2.9 kg), and fatty liver index (- 8.7) were observed. In patients with normal liver function at baseline, no clinically significant changes in AST and ALT were observed. In patients with abnormal liver function at baseline, clinically and statistically significant decreases (P < 0.05 vs. baseline, two-sample t test) in AST (- 9.0 U/L) and ALT (- 14.7 U/L) levels were observed.

Conclusion: Ipragliflozin was effective and well tolerated in Japanese patients with T2DM over 12 months in the real-world clinical setting. Improvements in liver function parameters (AST and ALT) were observed in T2DM patients with abnormal liver function.

Trial registration: ClinicalTrials.gov identifier, NCT02479399.

Funding: Astellas Pharma Inc., Japan.

Keywords: Effectiveness; Ipragliflozin; Japan; Post-marketing surveillance; Safety; Sodium–glucose cotransporter 2 inhibitor; Type 2 diabetes mellitus.

Figures

Fig. 1
Fig. 1
Patient disposition
Fig. 2
Fig. 2
Changes in eGFR (a), HbA1c (b), fasting plasma glucose (c), and body weight (d) from baseline to 12 months. HbA1c glycated hemoglobin, eGFR estimated glomerular filtration rate, SD standard deviation
Fig. 3
Fig. 3
Changes in AST (a) and ALT (b) from baseline to 12 months in patients stratified by liver function status. ALT alanine aminotransferase, AST aspartate aminotransferase, SD standard deviation
Fig. 4
Fig. 4
Changes in fatty liver index from baseline to 12 months. SD standard deviation

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