Key result
Saxagliptin linked to ~2-fold higher sudden cardiac arrest or ventricular arrhythmia risk vs sitagliptin in Medicaid.
Why the study?
In vivo studies suggested arrhythmia risk may be greater with less selective dipeptidyl peptidase-4 inhibitors, but evidence from population-based studies was missing.
Does treatment with saxagliptin or linagliptin compared with sitagliptin increase the risk of sudden cardiac arrest or ventricular arrhythmia in adults with type 2 diabetes?
Cohort (n=120,867)
Yes
Does treatment with saxagliptin or linagliptin compared with sitagliptin increase the risk of sudden cardiac arrest or ventricular arrhythmia in adults with type 2 diabetes?
This large two-database cohort study found discordant results regarding whether saxagliptin increases the risk of sudden cardiac arrest and ventricular arrhythmia compared to sitagliptin (increased risk in Medicaid, null effect in Optum), whereas linagliptin showed no elevated risk.
Answers are grounded in this paper and cite their sources.
Discordant database findings should not change DPP-4 inhibitor selection; leaves open saxagliptin's arrhythmic risk.
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.
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Dawwas et al. (2021) conducted a cohort in Type 2 diabetes (n=120,867). Saxagliptin (and linagliptin in Optum) vs. Sitagliptin was evaluated on Outpatient-originating sudden cardiac arrest (SCA) or ventricular arrhythmia (VA) defined by first-listed emergency department or principal inpatient discharge diagnosis codes (HR 2.01, 95% CI 1.24-3.25). Saxagliptin was associated with a higher rate of sudden cardiac arrest or ventricular arrhythmia vs sitagliptin in Medicaid (aHR 2.01, 95% CI 1.24-3.25), though not in Optum (aHR 0.79).
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