Key result
GLP-1 RAs are linked to an ~18% lower risk of major events versus SGLT2 inhibitors.
Why the study?
HFpEF and DM are interrelated conditions associated with high morbidity and mortality, prompting a comparison of the cardiovascular protective effects of GLP-1 RAs versus SGLT2 inhibitors in this population.
Do GLP-1 RAs reduce the risk of cardiovascular events compared to SGLT2 inhibitors in patients with HFpEF and diabetes mellitus?
Cohort (n=4,354)
Do GLP-1 RAs reduce the risk of cardiovascular events compared to SGLT2 inhibitors in patients with HFpEF and diabetes mellitus?
Effect estimate: HR 0.825 (95% CI 0.717-0.950)
In a retrospective matched cohort of patients with HFpEF and diabetes, GLP-1 RAs were associated with superior cardiovascular protection compared to SGLT2 inhibitors over 3 years.
Supports GLP-1 RA preference over SGLT2i in HFpEF with diabetes; hypothesis-generating, should not yet change practice.
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and diabetes mellitus (DM) are interrelated conditions associated with high morbidity and mortality. This study compared the cardiovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus sodium-glucose cotransporter-2 (SGLT2) inhibitors in this population. METHODS: This retrospective cohort study used data from the TriNetX database. It included 2,177 matched pairs of patients with HFpEF and DM treated with either GLP-1 RAs or SGLT2 inhibitors. Outcomes assessed over three years were a composite of all-cause mortality and progression to systolic heart failure, acute myocardial infarction, or stroke. RESULTS: GLP-1 RAs significantly reduced the risk of composite outcomes at one year (Hazard Ratio, HR 0.784; 95% CI, 0.658-0.934), two years (HR 0.813; 95% CI, 0.702-0.941), and three years (HR 0.825; 95% CI, 0.717-0.950). Specifically, GLP-1 RAs showed significantly reduced risks of progression to systolic heart failure (HR 0.60) and stroke (HR 0.75) compared to SGLT2 inhibitors. These protective effects were most pronounced in the first year and showed a slightly diminishing trend. While not statistically significant, GLP-1 RAs also exhibited a trend towards fewer myocardial infarctions (HR 0.83) and lower mortality rates (HR 0.83) than SGLT2 inhibitors. Subgroup analyses revealed more significant benefits in patients aged ≥60, women, Caucasians, those without moderate-to-severe chronic kidney disease or chronic ischemic heart disease, and those with better-controlled DM. CONCLUSIONS: Among HFpEF patients with DM, GLP-1 RAs demonstrated superior cardiovascular protective effects compared with SGLT2 inhibitors over a 3-year follow-up period. Further randomized trials are required to confirm these findings.
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Li et al. (2025) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF) and diabetes mellitus (DM) (n=4,354). GLP-1 RAs vs. SGLT2 inhibitors was evaluated on Composite of all-cause mortality and progression to systolic heart failure, acute myocardial infarction, or stroke (HR 0.825, 95% CI 0.717-0.950). GLP-1 RAs significantly reduced the 3-year risk of a composite of mortality, progression to systolic heart failure, MI, or stroke compared to SGLT2 inhibitors (HR 0.825; 95% CI 0.717-0.950).
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