Oral Semaglutide and Heart Failure: SOUL Secondary Analysis

In a secondary analysis of the randomized SOUL trial, oral semaglutide was associated with a lower risk of serious heart-failure events (vs placebo) among participants with type 2 diabetes who had pre-existing heart failure.

The SOUL trial enrolled nearly 9,650 adults with type 2 diabetes and either established cardiovascular disease or chronic kidney disease, and followed them for nearly four years. Participants were randomized to oral semaglutide or placebo, and results differed by baseline heart-failure status.

The report defines its composite “serious heart failure” endpoint as heart failure hospitalization, an urgent heart failure visit, or cardiovascular death. Among participants with a history of heart failure, those assigned to oral semaglutide were about 22% less likely than those assigned to placebo to experience the composite outcome. The central observation was a lower risk signal confined to the subgroup with prior heart failure.

Beyond prior heart-failure status, the apparent benefit was especially notable among participants described as having heart failure with preserved ejection fraction (HFpEF), and it also reports that participants without a prior history of heart failure did not have a significant reduction in heart-failure events.

Taken together, the report frames these points as observations from a secondary heart-failure analysis within a broader cardiovascular outcomes trial.

Key Takeaways:

• A randomized trial of nearly 9,650 adults with type 2 diabetes and established cardiovascular disease or chronic kidney disease were followed for nearly four years.
• In a secondary analysis described by the report, participants with prior heart failure randomized to oral semaglutide had a lower reported risk of the composite “serious heart failure” endpoint than those receiving placebo.
• The article highlights HFpEF as a subgroup with an especially notable signal, reports no significant reduction without prior heart failure, and includes investigator statements on safety in diabetes with heart failure and the convenience of a once-daily oral formulation.