The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors

Abstract

Purpose: Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduced the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal cohort of diabetic patients. Methods: We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 21,480 and 22,989 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results: Overall, 56%, 42%, and 2% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (4%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [adjusted hazard ratio: 0.69; 95% confidential interval: 0.64-0.74; P < 0.001]. Subgroup analysis revealed that the use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i across several subgroups including old age, the presence of congestive heart failure, cardiovascular disease, overweight patients, hemoglobin A1c 8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i. Conclusions: SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.

SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system

“…The CVD-Real Nordic, a retrospective observational study (n = 40,908 patients) performed in Denmark, Norway and Sweden, reported no difference in the incidence of AF among patients who received SGLT2i versus matched patients who received DPP-4 inhibitors [13] or other glucose-lowering medications [12]. On the other side, a study from Taiwan reported markedly lower rates of AF among 15,606 new users of SGLT2i versus 12,383 new users of DPP-4 inhibitors, after inverse probability of treatment weighting [14]. In view of these conflicting results, more real-world data are needed to verify whether the protection exerted by SGLT2i against AF observed in trials could apply to clinical practice.…”

“…Thus, it is important that, in the absence of dedicated trials, potential benefits resulting from post-hoc trial analyses are confirmed in clinical practice. So far, limited real-world studies provided inconsistent results on the association between use of SGLT2i and rates of AF [12][13][14]. Spontaneous reports of adverse events (AE) populate large databases with clinically-relevant information emerging from clinical practice.…”