Comparative safety of dipeptidyl peptidase-4 inhibitors and sudden cardiac arrest and ventricular arrhythmia: Population-based cohort studies Journal Article


Authors: Dawwas, G. K.; Hennessy, S.; Brensinger, C. M.; Deo, R.; Bilker, W. B.; Soprano, S. E.; Dhopeshwarkar, N.; Flory, J. H.; Bloomgarden, Z. T.; Aquilante, C. L.; Kimmel, S. E.; Leonard, C. E.
Article Title: Comparative safety of dipeptidyl peptidase-4 inhibitors and sudden cardiac arrest and ventricular arrhythmia: Population-based cohort studies
Abstract: In vivo studies suggest that arrhythmia risk may be greater with less selective dipeptidyl peptidase-4 inhibitors, but evidence from population-based studies is missing. We aimed to compare saxagliptin, sitagliptin, and linagliptin with regard to risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA). We conducted high-dimensional propensity score (hdPS) matched, new-user cohort studies. We analyzed Medicaid and Optum Clinformatics separately. We identified new users of saxagliptin, sitagliptin (both databases), and linagliptin (Optum only). We defined SCA/VA outcomes using emergency department and inpatient diagnoses. We identified and then controlled for confounders via a data-adaptive, hdPS approach. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar year. We identified the following matched comparisons: saxagliptin vs. sitagliptin (23,895 vs. 96,972) in Medicaid, saxagliptin vs. sitagliptin (48,388 vs. 117,383) in Optum, and linagliptin vs. sitagliptin (36,820 vs. 78,701) in Optum. In Medicaid, use of saxagliptin (vs. sitagliptin) was associated with an increased rate of SCA/VA (adjusted HR (aHR), 2.01, 95% confidence interval (CI) 1.24–3.25). However, in Optum data, this finding was not present (aHR, 0.79, 95% CI 0.41–1.51). Further, we found no association between linagliptin (vs. sitagliptin) and SCA/VA (aHR, 0.65, 95% CI 0.36–1.17). We found discordant results regarding the association between SCA/VA with saxagliptin compared with sitagliptin in two independent datasets. It remains unclear whether these findings are due to heterogeneity of treatment effect in the different populations, chance, or unmeasured confounding. © 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics
Journal Title: Clinical Pharmacology & Therapeutics
Volume: 111
Issue: 1
ISSN: 0009-9236
Publisher: Nature Publishing Group  
Date Published: 2022-01-01
Start Page: 227
End Page: 242
Language: English
DOI: 10.1002/cpt.2381
PUBMED: 34331322
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 January 2022 -- Source: Scopus
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  1. James H Flory
    35 Flory