Oral semaglutide reduced NT-proBNP levels significantly more than no semaglutide in obesity-related HFpEF (-350 vs. -180 pg/mL; difference -160 pg/mL, 95% CI -233 to -87; P=0.032).
Cohort (n=145)
Does oral semaglutide reduce NT-proBNP levels in adults with obesity-related HFpEF?
In a real-world Indian cohort, oral semaglutide was associated with significant reductions in NT-proBNP and early improvements in functional measures over 4 weeks in patients with obesity-related HFpEF.
Effect estimate: between-group difference -160 pg/mL (95% CI -233 to -87)
Absolute Event Rate: -350% vs -180%
p-value: p=0.032
Abstract Background: While large multinational trials such as STEP-heart failure with preserved ejection fraction (HFpEF) have demonstrated benefits with subcutaneous semaglutide across diverse populations, real-world evidence on the oral formulation, particularly in Indian practice settings, remains limited. Objective: We aimed to assess the feasibility, short-term biomarker and functional responses, and tolerability of oral semaglutide in routine care of obesity-related HFpEF in India. Methods: We retrospectively analyzed 145 adults with obesity-related HFpEF who received oral semaglutide or no semaglutide. The primary endpoint was the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels from baseline to follow-up. Reassessments were performed at a mean of 4 ± 1 weeks (median 4 weeks) after baseline. The secondary endpoints included change in body mass index, New York Heart Association (NYHA) functional class, 6-min walk distance (6-MWD), and exploratory time-to-event outcomes. Oral semaglutide was initiated at 3 mg daily and titrated to 7–14 mg, as tolerated. Results: The semaglutide group showed a larger NT-proBNP reduction than controls (−350 vs. −180 pg/mL; P = 0.032), corresponding to a baseline-adjusted between-group difference of − 160 pg/mL (95% confidence interval CI: −233 to − 87). Associations were directionally consistent across diabetes status, and larger changes were observed at higher baseline NT-proBNP; no formal interaction testing was performed. NYHA improvement was numerically higher (38% vs. 24%; P = 0.03), although the risk difference 95% CI included zero. The 6-MWD increased by + 40 ± 15 m versus + 20 ± 12 m ( P = 0.04). Exploratory time-to-event analyses showed no statistically significant between-group differences over ≈ 4 weeks. Adverse events were mainly mild gastrointestinal symptoms. Conclusion: In this Indian real-world cohort, oral semaglutide was associated with lower NT-proBNP levels and early changes in functional measures over ≈ 4 weeks; these findings are hypothesis-generating and directionally consistent with international randomized controlled trials of subcutaneous semaglutide in HFpEF.
Vallapuri et al. (Thu,) conducted a cohort in Obesity-related heart failure with preserved ejection fraction (HFpEF) (n=145). Oral semaglutide vs. No semaglutide was evaluated on Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels from baseline to follow-up (between-group difference -160 pg/mL, 95% CI -233 to -87, p=0.032). Oral semaglutide reduced NT-proBNP levels significantly more than no semaglutide in obesity-related HFpEF (-350 vs. -180 pg/mL; difference -160 pg/mL, 95% CI -233 to -87; P=0.032).