The association between SGLT2 inhibitors and new-onset arrhythmias: a nationwide population-based longitudinal cohort study

Abstract

Background: Clinical trials have shown the cardiovascular protective effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors and reduced hospitalization for heart failure. However, no study has investigated the association between SGLT2 inhibitors and the risk of arrhythmias. This study aimed to evaluate the risk of new-onset arrhythmias (NOA) and all-cause mortality with the use of SGLT2 inhibitors. Methods: This was a population-based cohort study utilizing Taiwan's National Health Insurance Research Database. Each patient aged 20 years and older who took SGLT2 inhibitors was assigned to the SGLT2 inhibitor group, whereas sex-, age-, diabetes mellitus duration-, drug index date-, and propensity score-matched randomly selected patients without SGLT2 inhibitors were assigned to the non-SGLT2 inhibitor group. The study outcome was all-cause mortality and NOA. Results: A total of 399,810 patients newly diagnosed with type 2 DM were enrolled. A 1:1 matching propensity method was used to match 79,150 patients to 79,150 controls in the non-SGLT2 inhibitors group for analysis. The SGLT2 inhibitor group was associated with a lower risk of all-cause mortality [adjusted hazard ratio (aHR) 0.547; 95% confidence interval (CI) 0.482-0.621; P = 0.0001] and NOA (aHR 0.830; 95% CI 0.751-0.916; P = 0.0002). Conclusions: Patients with type 2 DM prescribed with SGLT2 inhibitors were associated with a lower risk of all-cause mortality and NOA compared with those not taking SGLT2 inhibitors in real-world practice.

Effects and safety of SGLT2 inhibitors compared to placebo in patients with heart failure: A systematic review and meta-analysis

“…Aside from clinical trials, some studies have estimated the impact of SGLT2i in the real-world setting [61] , [62] , [63] , [64] . Arnold et al [61] evaluated patients of the Diabetes Collaborative Registry, and described that 26.2% of patients met the inclusion criteria for taking SGLT2i, but only 5.2% did it, causing more death and hospitalization rates.…”

Cardioprotection of Sodium–Glucose Cotransporter 2 Inhibition in Rats With Isoproterenol-Induced Cardiomyopathy

“…Therefore, ISOinduced cardiotoxicity is one of the most widely studied model for chronic cardiac injury. Hung-Yi Chen et al [26] has reported that patients prescribed with SGLT2i were associated with a lower risk of new-onset arrhythmias compared with those not taking SGLT2 inhibitors in real-world practice. Therefore, we also studied the role of Dapa on VAs in ISO-treated rats.…”

“…At present, more attention was paid to the effects of SGLT2i on cardiovascular system [7][8]. A recent nationwide population-based longitudinal cohort study revealed that patients with type 2 diabetes prescribed with SGLT2i were associated with a lower risk of all-cause mortality and new-onset arrhythmias compared with those not taking SGLT2i in real-world practice [9]. Isoproterenol (ISO) as a synthetic nonselective β-adrenoceptor agonist is well accepted to induce myocardial damage in rats for evaluating cardiac dysfunctions [10].…”

SGLT2 inhibition and COVID‐19: The road not taken

“…Reduced ectopic fat in the pericardium (with dapagliflozin) and favourable alteration in cytokine profile (reduction in IL‐6, TNF‐α with canagliflozin) are other putative mechanisms that could mediate benefits in COVID‐19 11 . Recent evidence also suggests significant reduction in new‐onset arrhythmias (HR 0.83, P = .002) 12 and benefit in heart failure with preserved ejection fraction (not uncommon in patients with obesity and diabetes) with the use of SGLT2i. Apart from established benefits in chronic heart failure, evidence from clinical studies using empagliflozin and rodent models using dapagliflozin suggests cardioprotection (reduced infarct size and improved LV function) during acute decompensated heart failure and ischaemia‐reperfusion injury 13 …”