Article Text
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
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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.