You are here

  • Home
  • Archive
  • Volume 5, Issue 1
  • Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes

Article Text

Article menu

Download PDFPDF

XML
Epidemiology/Health Services Research
Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes
  1. Vincent Lo Re1,2,3,
  2. Dena M Carbonari1,2,
  3. M Elle Saine1,2,3,
  4. Craig W Newcomb1,
  5. Jason A Roy1,2,
  6. Qing Liu1,
  7. Qufei Wu1,
  8. Serena Cardillo3,
  9. Kevin Haynes1,2,4,
  10. Stephen E Kimmel1,2,3,
  11. Peter P Reese1,2,3,
  12. David J Margolis1,2,3,
  13. Andrea J Apter1,2,3,
  14. K Rajender Reddy2,3,
  15. Sean Hennessy1,2,
  16. Harshvinder Bhullar5,
  17. Arlene M Gallagher6,
  18. Daina B Esposito4,
  19. Brian L Strom1,2,7
  1. 1 Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  2. 2 Center for Pharmacoepidemiology Research and Training, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  3. 3 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  4. 4 HealthCore Inc., Wilmington, Delaware, USA
  5. 5 QuintilesIMS, London, UK
  6. 6 Clinical Practice Research Datalink, London, UK
  7. 7 Rutgers Biomedical & Health Sciences, Rutgers, The State University of New Jersey, Newark, New Jersey, USA
  1. Correspondence to Dr Vincent Lo Re; vincentl{at}mail.med.upenn.edu

Abstract

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.

  • saxagliptin
  • post-authorization safety study
  • type 2 diabetes mellitus

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/

https://doi.org/10.1136/bmjdrc-2017-000400

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors VLR and BLS developed the study concept and design. DMC, KH, SEK, PPR, DJM, AJA, KRR, HB, AMG and DBE participated in the acquisition of data. CWN, QL, QW and JAR performed statistical analyses. VLR, DMC, MES, CWN, SEK, PPR and BLS conducted interpretation of the data. VLR and DMC drafted the manuscript. All authors provided critical revisions of the manuscript. VLR is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    • Funding This study was funded by AstraZeneca and the study’s sponsors approved the protocol and had the right to provide non-binding comments on this manuscript, but were excluded from all analyses involving Medicare data.

    • Competing interests VLR, DMC, MES, CWN, JAR, QL, QW, SC, KH, SEK, PPR, DJM, AJA, KRR and BLS received funding from AstraZeneca through their employers. AMG and HB are employees of CPRD and THIN, respectively. KH and DBE are employees of HealthCore. SEK has consulted for Pfizer, Merck and Bayer, all unrelated to this manuscript.

    • Ethics approval This study was approved by the UK Independent Scientific Advisory Committees for CPRD (Protocol 10_149RMn) and THIN (Protocol 11-039V), Quorum Review Institutional Review Board for HIRD, and Institutional Review Boards of the University of Pennsylvania and Rutgers University. A data use agreement was obtained from the Centers for Medicare and Medicaid Services.

    • Provenance and peer review Not commissioned; externally peer reviewed.