# Assessing Potential Valve-Preserving Effects of SGLT2 Inhibitors in Degenerative Aortic Stenosis: A Propensity-Matched Study

## TL;DR

This study suggests that SGLT2 inhibitors may reduce mortality and valve replacement in patients with aortic stenosis, but more research is needed to confirm direct effects on valve disease.

## Contribution

The study explores a potential new role for SGLT2 inhibitors in slowing degenerative aortic stenosis progression through observational clinical outcomes.

## Key findings

- SGLT2 inhibitor use was associated with lower all-cause mortality and reduced need for aortic valve replacement.
- The study found decreased risks of cardiac arrest and end-stage kidney disease among SGLT2 inhibitor users.
- Findings suggest possible valve-preserving effects, though lack of echocardiographic data limits direct conclusions on valve progression.

## Abstract

What is the clinical question being addressed?
Among patients with aortic stenosis, is SGLT2 inhibitor therapy associated with differences in key clinical outcomes, including all-cause mortality and progression to aortic valve replacement?

Among patients with aortic stenosis, is SGLT2 inhibitor therapy associated with differences in key clinical outcomes, including all-cause mortality and progression to aortic valve replacement?

What is the main finding?
In patients with aortic stenosis, SGLT2 inhibitor therapy was associated with lower risks of mortality and aortic valve replacement (SAVR or TAVR). These observations raise the possibility of a favorable effect on the clinical trajectory of aortic stenosis; however, the findings should be interpreted as associative given the absence of systematic longitudinal assessment of valvular disease progression.

In patients with aortic stenosis, SGLT2 inhibitor therapy was associated with lower risks of mortality and aortic valve replacement (SAVR or TAVR). These observations raise the possibility of a favorable effect on the clinical trajectory of aortic stenosis; however, the findings should be interpreted as associative given the absence of systematic longitudinal assessment of valvular disease progression.

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors), initially developed for glycemic control in type 2 diabetes, have demonstrated robust cardiovascular and renal benefits. Emerging evidence suggests that these agents may also affect valvular pathobiology, particularly in degenerative aortic stenosis (AS), through anti-inflammatory and antifibrotic mechanisms. Objectives: This study evaluated whether SGLT2 inhibitor use is associated with improved clinical outcomes in degenerative AS, including all-cause mortality and the need for SAVR or TAVR, recognizing that these endpoints represent surrogate rather than direct measures of valve hemodynamic progression. Methods: A retrospective cohort analysis was conducted using TriNetX, a federated electronic medical record-based research network. Diagnoses are captured using ICD-9/ICD-10-CM codes and medications using ATC codes. Adults with non-rheumatic AS were stratified by SGLT2 inhibitors use. Propensity score matching (1:1) was performed to balance baseline characteristics between treated and untreated groups (n = 10,912 per group). Primary outcomes included all-cause mortality, TAVR, and SAVR during follow-up. Echocardiographic parameters (AVA, Vmax, mean gradient) were not systematically available. Results: After adjustment for comorbidities, SGLT2 inhibitor use was independently associated with lower all-cause mortality (6.15% vs. 9.34% HR 0.595; 95% CI 0.552–0.641; p < 0.001), TAVR (2.81% vs. 2.89% HR 0.835; 95% CI 0.746–0.934; p = 0.002), SAVR (1.28% vs. 1.90% HR 0.514; 95% CI 0.442–0.599; p < 0.001), cardiac arrest (0.82% vs. 1.21% HR 0.71; 95% CI 0.582–0.867; p < 0.001), and end-stage kidney disease (0.40% vs. 1.0% HR 0.292; 95% CI 0.222–0.384; p < 0.001). Although these associations may suggest slower disease progression, interpretation is limited by the lack of systematic echocardiographic follow-up. Conclusions: In addition to their established benefits in heart failure and renal protection, SGLT2 inhibitors may have valve-preserving effects in degenerative AS. Because true hemodynamic progression could not be evaluated, these results should be viewed as associations with surrogate clinical endpoints. Prospective studies with standardized imaging are required to determine whether SGLT2 inhibition can directly alter the course of this currently untreatable disease