SGLT2 Inhibitors and Risk of Incident Atrial Fibrillation in Older Adults with Type 2 Diabetes

Type 2 diabetes (T2D) is associated with a 35 to 60% increase in the risk of developing atrial fibrillation (AF). Atrial fibrillation in older adults is associated with substantial morbidity and mortality.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiorenal benefits for patients with T2D in large cardiovascular outcome trials. However, the role of this class with respect to the risk of incident AF remains less understood.

In a post-hoc analysis of the DECLARE-TIMI 58 trial, dapagliflozin reduced the incidence of AF by 19% in patients with T2D compared with placebo. A possible protective effect of SGLT2i for AF has been reported in a meta-analysis, however, AF was not a pre-specified endpoint in the included randomized control trials (RCTs), and it was typically reported as an adverse event, further limiting the ability to assess this outcome in a robust way. In addition, incident AF was not a common event in the RCTs and was mostly evaluated in patients younger than 65 years.

SGLT2i may reduce AF through multiple mechanisms

SGLT2i may promote natriuresis and diuresis and thus may decrease atrial dilation. SGLT2i may reduce mitochondrial dysfunction and atrial remodeling, and therefore they reduce AF susceptibility. SGLT2i have also been shown to lower blood pressure, body weight, inflammation, and oxidative stress, all of which play an important role in promoting AF.

Association between SGLT2i initiation and incident AF

The study presented by Dr. Elisabetta Patorno assessed the association between SGLT2i initiation and incident AF compared with the initiation of alternative anti-diabetic medications in a nationwide cohort of older adults with type 2 diabetes. The study was conducted using the Medicare fee-for-service, which is a US nationwide electronic healthcare database of federally insured Americans aged ≥65.

The study compared SGLT2i with dipeptidyl peptidase 4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The study population included patients over 65 years with T2D, initiated on SGLT2i, or comparative medication, DPP-4 inhibitors, or GLP-1 RA between April 2013 and December 2018. Patients were required to be truly new initiators – they were required to have at least 12 months of continuous baseline enrollment prior to cohort entry without any use of SGLT2i or the specific comparator. The primary outcome was incident atrial fibrillation, which was defined as hospitalization with a discharge diagnosis for AF, based on a validated algorithm.

SGLT2i initiation may be beneficial in older adults with T2D

Compared with DPP-4 inhibitors, the initiation of SGLT2i was associated with an 18% reduction in the risk of AF hospitalization corresponding to approximately 4 fewer keys for 1000 person-years for AF hospitalization. Compared with GLP-1RA, initiation of SGLT2i was associated with a 10% reduction in the risk of AF hospitalization, which corresponded to approximately 2 fewer cases per 1000 person-years for this outcome. There was no evidence of meaningful effect modification by age, sex, history of our failure, or history of ASCVD.

The study concludes that the initiation of SGLT2i may be beneficial in older adults with T2D who are at risk for AF in clinical practice.

Reference

Elisabetta Patorno. 177-OR: SGLT2 Inhibitors and Risk of Incident Atrial Fibrillation in Older Adults with Type 2 Diabetes. Oral presentation at: American Diabetes Association 82nd Scientific Sessions; June, 2022.