Oral Semaglutide and Change in Cardiovascular Risk Factors in High-Risk Type 2 Diabetes: A Post Hoc Secondary Analysis of the SOUL Randomized Clinical Trial

What Was Tested

This randomized controlled trial paper looks at Semaglutide.

Individuals with type 2 diabetes (T2D) are at high risk of atherosclerotic cardiovascular disease (ASCVD).

Who Took Part

PubMed indexes the participants as middle-aged adults and older adults, both men and women.

This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC.

Participants underwent randomization from June 2019 to March 2021, with a mean (SD) of 47.5 (10.9) months of follow-up, and data were analyzed from February to December 2025.

How the Study Was Run

The researchers set it up as a randomized, double-blind, placebo-controlled and multicenter study.

The participants were allocated by chance, so the Semaglutide group and the comparison group should start out alike.

Neither the participants nor the staff measuring them knew who was on Semaglutide, so expectations could not easily colour the readings.

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

More than one site took part, so the participants came from several places.

What Was Measured

PubMed files the paper under topics including Semaglutide, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Hypoglycemic Agents, Heart Disease Risk Factors, Cardiovascular Diseases and Glycated Hemoglobin.

What This Means in Plain Language

The paper is a randomized, double-blind and placebo-controlled study of Semaglutide.

Its findings take up roughly 7 sentences of the abstract and are left out here on purpose; the source paper is the place to read them.

The publication is from 2026 (JAMA cardiology), a journal based in United States.

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