Heart failure & cardiomyopathiesSecondary analysis
Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes
- secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial
- conducted at 444 centers in 33 countries
- stratified according to the presence or absence of heart failure (HF) history at baseline
Authors' conclusion
In this secondary analysis of the SOUL randomized clinical trial, among individuals with T2D, atherosclerotic CV disease, and/or chronic kidney disease, a reduction of HF events was observed with use of oral semaglutide compared with placebo in those with a history of HF, without increasing the risk of serious adverse events. These data support the potential benefit of oral semaglutide in reducing HF events in people with T2D and HF.
Study context
- Population
- Participants with T2D and atherosclerotic cardiovascular (CV) disease and/or chronic kidney disease, with or without HF history at baselinerandomized, 2229 (23.1%) had HF history · HF with preserved ejection fraction 991 · HF with reduced ejection fraction 592 · HF of unknown subtype 646
- Participants
- 9,650 participants
- Comparison
- oral semaglutide vs placebo
- Primary endpoint
- Prespecified composite HF outcome:
- Time to first occurrence of HF hospitalization
- Urgent HF visit
- CV death
- Follow-up
- Mean (SD) 47.5 (10.9) months
Primary result
As reported in the abstract
Oral semaglutide vs PlaceboHazard ratio (95% CI)
participants with HF at baseline
0.78(0.63–0.96)
participants without HF at baseline
1.01(0.84–1.20)
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Composite HF outcome among participants with HF, by ejection fraction (subgroup) — Oral semaglutide vs Placebo · preserved ejection fraction | 0.59 (0.39–0.86) | |
| Composite HF outcome among participants with HF, by ejection fraction (subgroup) — Oral semaglutide vs Placebo · reduced ejection fraction | 0.98 (0.70–1.38) | |
| MACE, by HF history — Oral semaglutide vs Placebo · with HF history | 0.83 (0.68–1.01) | |
| MACE, by HF history — Oral semaglutide vs Placebo · without HF history | 0.86 (0.75–0.98) | |
| 0.20.5125Hazard ratio (log scale) |
- MACE, by HF history: P for interaction = .77
MACE, by HF history
- No heterogeneity in the risk reduction of MACE
Safety
Serious adverse events among participants with HF
Serious adverse events among participants with HF
- similar
Original publication
Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes. JAMA Intern Med. Published 1 April 2026. doi:10.1001/jamainternmed.2025.7774
Summarised from the published abstract; every number is checked against it