Oral semaglutide and survival in heart failure with preserved ejection fraction and type 2 diabetes

Aims Heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D) commonly coexist and are associated with poor outcomes. Although injectable semaglutide has demonstrated benefits in HFpEF, the effectiveness of oral semaglutide in this setting remains uncertain. This study compared all‐cause death and hospitalisation between oral semaglutide and sitagliptin in patients with HFpEF and T2D. Materials and Methods Using a global healthcare data and analytics platform, the TriNetX research network, we conducted a retrospective multi‐centre observational study. We identified patients aged ≥18 years with HFpEF diagnosed before December 31, 2023 ( N = 1 731 548), of whom 812 259 had concomitant T2D. Among them, 3470 initiated oral semaglutide and 22 840 initiated sitagliptin between October 1, 2019, and December 31, 2023. After propensity score matching, each group included 3452 patients. The primary outcome was all‐cause death; the secondary outcome was hospitalisation. Results Over 1 year, the risk for all‐cause death in patients who received oral semaglutide relative to those who received sitagliptin was significantly lower (4.3% [145/3452] vs. 7.0% [229/3452]; log‐rank p < 0.001; hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.50 to 0.75). Similarly, patients who received oral semaglutide experienced fewer hospitalisations than those who received sitagliptin (37.1% vs. 42.4%; log‐rank p < 0.001; HR, 0.83; 95% CI, 0.77 to 0.90). Conclusions Oral semaglutide appeared to be associated with a lower 1‐year risk of all‐cause death compared with sitagliptin in patients with HFpEF and T2D.