Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial

What Was Tested

Researchers studied Semaglutide in this randomized controlled trial publication.

However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03914326.

Who Took Part

The abstract describes 9650 participants taking part.

By PubMed's age tags, the people studied were middle-aged adults and older adults, both men and women.

The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo.

As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932).

How the Study Was Run

In design terms this was a randomized and placebo-controlled study.

Random assignment meant chance, not the researchers, decided who got Semaglutide and who got the comparison, which limits bias.

Some participants received a placebo instead of Semaglutide, giving a reference point.

Safety was evaluated by comparing the incidence of serious adverse events.

What Was Measured

However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes.

PubMed files the paper under topics including Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide 1 and Semaglutide.

Author keywords: cardiovascular system, glucagon-like peptide-1 receptor agonists and renal insufficiency, chronic.

What This Means in Plain Language

The paper is a randomized and placebo-controlled study of Semaglutide in 9650 participants.

With several hundred people or more, it is a fairly large study for this kind of research.

Results are reported in around 5 sentences of the abstract; we leave them to the paper itself rather than summarise them.

The publication is from 2025 (Circulation), a journal based in United States.

More context: the Semaglutide compound page, all human trials.