Postauthorization safety study of the DPP-4 inhibitor saxagliptin: a large-scale multinational family of cohort studies of five outcomes

Vincent Lo Re, Dena M Carbonari, M Elle Saine, Craig W Newcomb, Jason A Roy, Qing Liu, Qufei Wu, Serena Cardillo, Kevin Haynes, Stephen E Kimmel, Peter P Reese, David J Margolis, Andrea J Apter, K Rajender Reddy, Sean Hennessy, Harshvinder Bhullar, Arlene M Gallagher, Daina B Esposito, Brian L Strom, Vincent Lo Re, Dena M Carbonari, M Elle Saine, Craig W Newcomb, Jason A Roy, Qing Liu, Qufei Wu, Serena Cardillo, Kevin Haynes, Stephen E Kimmel, Peter P Reese, David J Margolis, Andrea J Apter, K Rajender Reddy, Sean Hennessy, Harshvinder Bhullar, Arlene M Gallagher, Daina B Esposito, Brian L Strom

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.

Keywords: post-authorization safety study; saxagliptin; type 2 diabetes mellitus.

Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Meta-analyses of HRs (with 95% CIs) of hospitalization with and/or death due to a major adverse cardiovascular event (A), hospitalization for acute kidney injury (B), and hospitalization for infection (C) across the data sources. CPRD, Clinical Practice Research Datalink; HIRD, HealthCore Integrated Research Database; THIN, The Health Improvement Network.

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