(A-078) Comparative Effectiveness of GLP-1 Receptor Agonists and SGLT2 Inhibitors in Heart Failure with Preserved Ejection Fraction: A Network Meta-Analysis

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may provide potential cardiovascular benefits for patients with heart failure with preserved ejection fraction (HFpEF). However, direct comparisons between GLP-1RAs and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in this population remain limited.

Objectives: This network meta-analysis aimed to compare the effectiveness of GLP-1RAs and SGLT2is in patients with HFpEF.

Methods: A network meta-analysis was conducted using data from five randomized controlled trials (RCTs) evaluating GLP-1RAs or SGLT2is versus placebo in HFpEF patients. The outcome of interest was a composite of heart failure hospitalization and cardiovascular death (HHF/CV death). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Pairwise and network meta-analysis with a random-effects model.

Results: A total of 14,127 patients with HFpEF from five RCTs were included, with three trials evaluating GLP-1RAs and two evaluating SGLT2is. The results from pairwise meta-analysis showed that SGLT2is were significantly associated with a reduced risk of HHF/CV death (HR: 0.83, 95% CI: 0.76–0.89), while GLP-1RAs did not show a statistically significant association (HR: 0.41, 95% CI: 0.15–1.08). However, in network meta-analysis, both GLP-1RAs (HR: 0.56, 95% CI: 0.39–0.80) and SGLT2is (HR: 0.83, 95% CI: 0.73–0.93) were significantly associated with reduced HHF/CV death risk. GLP-1RAs seem to have a lower risk compared to SGLT2is (HR: 0.68, 95% CI: 0.46–0.99).

Conclusions: This study highlights the established benefit of SGLT2is in reducing HHF/CV death in patients with HFpEF, while suggesting a potential benefit of GLP-1RAs in this population. Further direct head-to-head studies are needed to clarify their comparative effectiveness.