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Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial

AIM: To assess the efficacy and safety of once‐daily ipragliflozin 50 mg versus placebo in Japanese people with type 1 diabetes mellitus (T1DM) inadequately controlled with insulin. MATERIALS AND METHODS: We conducted a multicentre, double‐blind, parallel‐group, placebo‐controlled phase 3 study. Par...

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Detalles Bibliográficos
Autores principales: Kaku, Kohei, Isaka, Hiroyuki, Sakatani, Taishi, Toyoshima, Junko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772182/
https://www.ncbi.nlm.nih.gov/pubmed/31173455
http://dx.doi.org/10.1111/dom.13807
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author Kaku, Kohei
Isaka, Hiroyuki
Sakatani, Taishi
Toyoshima, Junko
author_facet Kaku, Kohei
Isaka, Hiroyuki
Sakatani, Taishi
Toyoshima, Junko
author_sort Kaku, Kohei
collection PubMed
description AIM: To assess the efficacy and safety of once‐daily ipragliflozin 50 mg versus placebo in Japanese people with type 1 diabetes mellitus (T1DM) inadequately controlled with insulin. MATERIALS AND METHODS: We conducted a multicentre, double‐blind, parallel‐group, placebo‐controlled phase 3 study. Participants (N = 175) were randomized (2:1) to receive once‐daily ipragliflozin 50 mg (n = 115) or placebo (n = 60), combined with insulin, for 24 weeks. The primary endpoint was change in glycated haemoglobin (HbA1c); key secondary endpoints included change in insulin dose and body weight. Treatment‐emergent adverse events (TEAEs) were evaluated. RESULTS: The ipragliflozin group demonstrated a significant decrease in HbA1c from baseline to end of treatment versus the placebo group: adjusted mean difference (AMD) −3.8 mmol/mol (95% confidence interval [CI] −6.2, −1.5) or − 0.36% (95% CI −0.57, −0.14; P = 0.001). Significant reductions in total daily insulin dose (AMD −7.35 IU [95% CI −9.09, −5.61]; P < 0.001) and body weight (AMD −2.87 kg [95% CI −3.58, −2.16]; P < 0.001) were observed for the ipragliflozin group versus placebo. Two serious TEAEs occurred (major hypoglycaemia and abdominal abscess); both were in the placebo group. All other TEAEs were mild or moderate in severity. Four cases of study discontinuation occurred; three in the placebo group and one in the ipragliflozin group. No diabetic ketoacidosis was reported for any participant in this study. CONCLUSIONS: Daily ipragliflozin 50 mg in combination with insulin significantly reduced HbA1c, daily insulin dose and body weight versus placebo in people with T1DM. No safety concerns were identified after 24 weeks of treatment. Overall, once‐daily ipragliflozin 50 mg was both efficacious and well tolerated.
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spelling pubmed-67721822019-10-07 Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial Kaku, Kohei Isaka, Hiroyuki Sakatani, Taishi Toyoshima, Junko Diabetes Obes Metab Original Articles AIM: To assess the efficacy and safety of once‐daily ipragliflozin 50 mg versus placebo in Japanese people with type 1 diabetes mellitus (T1DM) inadequately controlled with insulin. MATERIALS AND METHODS: We conducted a multicentre, double‐blind, parallel‐group, placebo‐controlled phase 3 study. Participants (N = 175) were randomized (2:1) to receive once‐daily ipragliflozin 50 mg (n = 115) or placebo (n = 60), combined with insulin, for 24 weeks. The primary endpoint was change in glycated haemoglobin (HbA1c); key secondary endpoints included change in insulin dose and body weight. Treatment‐emergent adverse events (TEAEs) were evaluated. RESULTS: The ipragliflozin group demonstrated a significant decrease in HbA1c from baseline to end of treatment versus the placebo group: adjusted mean difference (AMD) −3.8 mmol/mol (95% confidence interval [CI] −6.2, −1.5) or − 0.36% (95% CI −0.57, −0.14; P = 0.001). Significant reductions in total daily insulin dose (AMD −7.35 IU [95% CI −9.09, −5.61]; P < 0.001) and body weight (AMD −2.87 kg [95% CI −3.58, −2.16]; P < 0.001) were observed for the ipragliflozin group versus placebo. Two serious TEAEs occurred (major hypoglycaemia and abdominal abscess); both were in the placebo group. All other TEAEs were mild or moderate in severity. Four cases of study discontinuation occurred; three in the placebo group and one in the ipragliflozin group. No diabetic ketoacidosis was reported for any participant in this study. CONCLUSIONS: Daily ipragliflozin 50 mg in combination with insulin significantly reduced HbA1c, daily insulin dose and body weight versus placebo in people with T1DM. No safety concerns were identified after 24 weeks of treatment. Overall, once‐daily ipragliflozin 50 mg was both efficacious and well tolerated. Blackwell Publishing Ltd 2019-07-11 2019-10 /pmc/articles/PMC6772182/ /pubmed/31173455 http://dx.doi.org/10.1111/dom.13807 Text en © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Kaku, Kohei
Isaka, Hiroyuki
Sakatani, Taishi
Toyoshima, Junko
Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial
title Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial
title_full Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial
title_fullStr Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial
title_full_unstemmed Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial
title_short Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial
title_sort efficacy and safety of ipragliflozin add‐on therapy to insulin in japanese patients with type 1 diabetes mellitus: a randomized, double‐blind, phase 3 trial
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772182/
https://www.ncbi.nlm.nih.gov/pubmed/31173455
http://dx.doi.org/10.1111/dom.13807
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