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Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes
OBJECTIVE: To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. RESEARCH DESIGN AND METHODS: Cohort studies using 2009–2014 data...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574452/ https://www.ncbi.nlm.nih.gov/pubmed/28878934 http://dx.doi.org/10.1136/bmjdrc-2017-000400 |
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author | Lo Re, Vincent Carbonari, Dena M Saine, M Elle Newcomb, Craig W Roy, Jason A Liu, Qing Wu, Qufei Cardillo, Serena Haynes, Kevin Kimmel, Stephen E Reese, Peter P Margolis, David J Apter, Andrea J Reddy, K Rajender Hennessy, Sean Bhullar, Harshvinder Gallagher, Arlene M Esposito, Daina B Strom, Brian L |
author_facet | Lo Re, Vincent Carbonari, Dena M Saine, M Elle Newcomb, Craig W Roy, Jason A Liu, Qing Wu, Qufei Cardillo, Serena Haynes, Kevin Kimmel, Stephen E Reese, Peter P Margolis, David J Apter, Andrea J Reddy, K Rajender Hennessy, Sean Bhullar, Harshvinder Gallagher, Arlene M Esposito, Daina B Strom, Brian L |
author_sort | Lo Re, Vincent |
collection | PubMed |
description | OBJECTIVE: To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. RESEARCH DESIGN AND METHODS: Cohort studies using 2009–2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare). All eligible adult patients newly prescribed saxagliptin (n=110 740) and random samples of up to 10 matched initiators of non-DPP-4 inhibitor OADs within each data source were selected (n=913 384). Outcomes were hospitalized major adverse cardiovascular events (MACE), acute kidney injury (AKI), acute liver failure (ALF), infections, and severe hypersensitivity events, evaluated using diagnostic coding algorithms and medical records. Cox regression was used to determine HRs with 95% CIs for each outcome. Meta-analyses across data sources were performed for each outcome as feasible. RESULTS: There were no increased incidence rates or risk of MACE, AKI, ALF, infection, or severe hypersensitivity reactions among saxagliptin initiators compared with other OAD initiators within any data source. Meta-analyses demonstrated a reduced risk of hospitalization/death from MACE (HR 0.91, 95% CI 0.85 to 0.97) and no increased risk of hospitalization for infection (HR 0.97, 95% CI 0.93 to 1.02) or AKI (HR 0.99, 95% CI 0.88 to 1.11) associated with saxagliptin initiation. ALF and hypersensitivity events were too rare to permit meta-analysis. CONCLUSIONS: Saxagliptin initiation was not associated with increased risk of MACE, infection, AKI, ALF, or severe hypersensitivity reactions in clinical practice settings. TRIAL REGISTRATION NUMBER: NCT01086280, NCT01086293, NCT01086319, NCT01086306, and NCT01377935; Results. |
format | Online Article Text |
id | pubmed-5574452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55744522017-09-06 Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes Lo Re, Vincent Carbonari, Dena M Saine, M Elle Newcomb, Craig W Roy, Jason A Liu, Qing Wu, Qufei Cardillo, Serena Haynes, Kevin Kimmel, Stephen E Reese, Peter P Margolis, David J Apter, Andrea J Reddy, K Rajender Hennessy, Sean Bhullar, Harshvinder Gallagher, Arlene M Esposito, Daina B Strom, Brian L BMJ Open Diabetes Res Care Epidemiology/Health Services Research OBJECTIVE: To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. RESEARCH DESIGN AND METHODS: Cohort studies using 2009–2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare). All eligible adult patients newly prescribed saxagliptin (n=110 740) and random samples of up to 10 matched initiators of non-DPP-4 inhibitor OADs within each data source were selected (n=913 384). Outcomes were hospitalized major adverse cardiovascular events (MACE), acute kidney injury (AKI), acute liver failure (ALF), infections, and severe hypersensitivity events, evaluated using diagnostic coding algorithms and medical records. Cox regression was used to determine HRs with 95% CIs for each outcome. Meta-analyses across data sources were performed for each outcome as feasible. RESULTS: There were no increased incidence rates or risk of MACE, AKI, ALF, infection, or severe hypersensitivity reactions among saxagliptin initiators compared with other OAD initiators within any data source. Meta-analyses demonstrated a reduced risk of hospitalization/death from MACE (HR 0.91, 95% CI 0.85 to 0.97) and no increased risk of hospitalization for infection (HR 0.97, 95% CI 0.93 to 1.02) or AKI (HR 0.99, 95% CI 0.88 to 1.11) associated with saxagliptin initiation. ALF and hypersensitivity events were too rare to permit meta-analysis. CONCLUSIONS: Saxagliptin initiation was not associated with increased risk of MACE, infection, AKI, ALF, or severe hypersensitivity reactions in clinical practice settings. TRIAL REGISTRATION NUMBER: NCT01086280, NCT01086293, NCT01086319, NCT01086306, and NCT01377935; Results. BMJ Publishing Group 2017-07-31 /pmc/articles/PMC5574452/ /pubmed/28878934 http://dx.doi.org/10.1136/bmjdrc-2017-000400 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Epidemiology/Health Services Research Lo Re, Vincent Carbonari, Dena M Saine, M Elle Newcomb, Craig W Roy, Jason A Liu, Qing Wu, Qufei Cardillo, Serena Haynes, Kevin Kimmel, Stephen E Reese, Peter P Margolis, David J Apter, Andrea J Reddy, K Rajender Hennessy, Sean Bhullar, Harshvinder Gallagher, Arlene M Esposito, Daina B Strom, Brian L Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes |
title | Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes |
title_full | Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes |
title_fullStr | Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes |
title_full_unstemmed | Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes |
title_short | Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes |
title_sort | postauthorization safety study of the dpp-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes |
topic | Epidemiology/Health Services Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574452/ https://www.ncbi.nlm.nih.gov/pubmed/28878934 http://dx.doi.org/10.1136/bmjdrc-2017-000400 |
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