Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a 36-week, open-label extension of a 16-week, randomized, placebo-controlled, double-blind study
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To examine long-term efficacy/safety of ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, added to ongoing insulin therapy in Japanese patients with type 2 diabetes.
We conducted a 36-week, open-label extension of ipragliflozin therapy following a 16-week, randomized, placebo-controlled, double-blind period (treatment periods II and I, respectively). Prior to the open-label period, patients taking insulin with/without a dipeptidyl peptidase-4 (DPP-4) inhibitor were randomized to receive placebo or 50 mg once-daily ipragliflozin. Oral antidiabetic drugs other than DPP-4 inhibitors were discontinued 4 weeks before screening. Following treatment period I, all patients received open-label ipragliflozin 50 mg, with the possibility of a dose increase to 100 mg at week 24 if HbA1c was ≥ 7.0% at week 20. Efficacy endpoints were changes in HbA1c, fasting plasma glucose (FPG), self-monitored blood glucose, bodyweight, and metabolic hormones. Drug-related treatment-emergent adverse events (TEAEs) were monitored for safety.
Of 175 patients randomized to ipragliflozin, 168 entered treatment period II, 121 (69%) of whom completed this period. The mean ± standard deviation changes in HbA1c, FPG, and bodyweight from baseline (start of treatment period I) to the end of treatment were − 0.83 ± 0.72%, − 31.5 ± 41.2 mg/dL, and − 1.34 ± 1.80 kg, respectively. Between weeks 8 and 32, HbA1c was lower in patients taking a DPP-4 inhibitor than in those without. The most common drug-related TEAE was hypoglycemia; no drug-related TEAEs not already reported for ipragliflozin were observed.
Ipragliflozin was well tolerated, effective, and reduced bodyweight over a period of 52 weeks in patients treated with insulin with/without a DPP-4 inhibitor.
KeywordsDipeptidyl peptidase-4 inhibitor Insulin Ipragliflozin Sodium–glucose cotransporter 2 inhibitor Type 2 diabetes mellitus
The authors wish to thank all of the investigators involved in this trial, as well as Nicholas Smith, PhD, and William Ng, MB, BS, PhD, of Edanz Medical Writing for providing medical writing services.
HI, SA, and TS contributed to study design, data analysis, and writing of the manuscript; SY and IN contributed to study design, study conduct, data collection and analysis, and writing of the manuscript.
This study was sponsored by Astellas Pharma Inc. Medical writing and editorial support was funded by Astellas Pharma Inc. and provided by Dr. Nicholas D. Smith and Dr. William Ng (Edanz Medical Writing) and Elsevier/ELMCOM™.
Compliance with ethical standards
Conflict of interests
HI has served on the scientific advisory board of Astellas Pharma Inc.; received lecture or consulting fees from Astellas Pharma Inc., MSD, Sanofi, Mitsubishi Tanabe Pharma, Boehringer Ingelheim Japan, and Novartis Pharma; and received grants/research support from Astellas Pharma Inc., Ono Pharmaceutical, Boehringer Ingelheim Japan, AstraZeneca, Sanofi, Mitsubishi Tanabe Pharma, Eli Lilly Japan, Daiichi-Sankyo, Novo Nordisk Pharma, Kyowa Hakko Kirin, and MSD. SY, IN, SA, and TS are employees of Astellas Pharma Inc., Japan.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.
Informed consent or substitute for it was obtained from all patients for being included in the study. The study was approved by the institutional review board at each participating site.
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