Among patients with newly diagnosed atrial fibrillation, baseline SGLT2 inhibitor use was not significantly associated with lower risks of cerebrovascular events or major adverse cardiovascular events, though a time-dependent analysis suggested lower all-cause mortality that should be interpreted cautiously because of potential residual confounding.
Key Findings
Results
Baseline SGLT2 inhibitor use was not significantly associated with the primary composite cerebrovascular outcome in patients with newly diagnosed atrial fibrillation.
The primary outcome was a composite of ischemic stroke, hemorrhagic stroke, or transient ischemic attack.
Adjusted hazard ratio was 0.90 (95% CI, 0.70–1.15; P=0.39).
Analysis included 1901 SGLT2 inhibitor users matched 1:10 to 19,010 nonusers.
The matched cohort had a mean age of 72 years, 41% women, and mean CHA2DS2-VASc score of 3.7.
Results
Baseline SGLT2 inhibitor use was not significantly associated with all-cause mortality in patients with newly diagnosed atrial fibrillation.
Adjusted hazard ratio for all-cause mortality was 0.95 (95% CI, 0.86–1.06; P=0.38).
This was a secondary outcome of the study.
The analysis used propensity score matching 1:10 of SGLT2 inhibitor users to nonusers.
Results
Baseline SGLT2 inhibitor use was not significantly associated with major adverse cardiovascular events in patients with newly diagnosed atrial fibrillation.
Adjusted hazard ratio for major adverse cardiovascular events was 0.94 (95% CI, 0.84–1.05; P=0.24).
Major adverse cardiovascular events were a secondary outcome.
Results were consistent with the null findings for the primary cerebrovascular composite outcome.
Results
A time-dependent sensitivity analysis found that current SGLT2 inhibitor exposure was associated with lower all-cause mortality.
Adjusted hazard ratio for all-cause mortality in the time-dependent analysis was 0.71 (95% CI, 0.63–0.81; P<0.01).
The authors noted this finding 'should be interpreted cautiously because of potential residual confounding.'
This analysis differed from the primary baseline-exposure analysis in that it accounted for ongoing versus discontinued SGLT2 inhibitor use over follow-up.
The discrepancy between the baseline and time-dependent analyses highlights the potential influence of immortal time bias or time-varying confounding.
Methods
The study identified 231,030 eligible patients with newly diagnosed atrial fibrillation from Taiwan's National Health Insurance Research Database between 2013 and 2022, of whom 20,911 were included in the matched analysis.
Data source was Taiwan's National Health Insurance Research Database.
Study period spanned 2013 through 2022.
Regular SGLT2 inhibitor users were propensity score matched 1:10 to nonusers, yielding 1901 users and 19,010 nonusers.
Mean age of the matched cohort was 72 years, 41% were women, and mean CHA2DS2-VASc score was 3.7.
Conclusions
The authors concluded that SGLT2 inhibitors should not be considered an alternative to guideline-directed oral anticoagulation for stroke prevention in atrial fibrillation.
The paper states 'SGLT2 inhibitors should not be considered an alternative to guideline-directed oral anticoagulation, which remains the cornerstone of stroke prevention in eligible patients with AF.'
This conclusion was supported by the lack of significant association between SGLT2 inhibitor use and cerebrovascular outcomes.
The finding aligns with existing guidelines that prioritize anticoagulation for AF-related stroke prevention.
What This Means
This research suggests that a class of diabetes medications called SGLT2 inhibitors — which have shown promise in reducing the initial development of atrial fibrillation (an irregular heart rhythm) and improving outcomes in heart failure — do not appear to significantly reduce the risk of strokes or other major cardiovascular events in people who have already been diagnosed with atrial fibrillation. The study used a large nationwide database from Taiwan covering nearly a decade, examining over 230,000 patients newly diagnosed with atrial fibrillation and carefully comparing those who used SGLT2 inhibitors to those who did not, using statistical matching to make the groups as similar as possible.
When researchers looked at whether patients were taking SGLT2 inhibitors at the start of the study, they found no meaningful reduction in stroke risk (including ischemic stroke, hemorrhagic stroke, and transient ischemic attack), overall death, or major cardiovascular events. A separate, more complex analysis that tracked whether patients were actively taking the medication over time did suggest a lower risk of death, but the authors caution that this finding may be due to other factors that were not fully accounted for, rather than a true drug effect.
This research matters because it clarifies that, despite the cardiovascular benefits of SGLT2 inhibitors in other settings, these drugs do not appear to replace the need for blood thinners (anticoagulants) in people with atrial fibrillation. Standard anticoagulation therapy remains the established approach for preventing strokes in eligible atrial fibrillation patients, and this study reinforces that SGLT2 inhibitors should not be viewed as a substitute for that treatment.
Huang T, Yap L, Lin H, Su P, Liao Y, Chen C, et al.. (2026). Sodium-Glucose Cotransporter-2 Inhibition in Patients With Newly Diagnosed Atrial Fibrillation: A Nationwide Cohort Study.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.049649