Topline results from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) have been reported, showing that oral semaglutide, a long-acting Glucagon-Like Peptide-1 (GLP-1) receptor agonist, significantly reduces the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes (T2D) who have established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).1
The phase 3, randomized, double-blind, parallel-group, placebo-controlled cardiovascular outcomes trial (NCT03914326) enrolled 9,650 adults aged 50 years or older. Participants were randomly assigned to receive either 14 mg of oral semaglutide or a placebo, in addition to standard care. Over the course of the trial, which began in 2019 and completed in 2021, oral semaglutide demonstrated a 14% reduction in the risk of MACE compared to placebo. In this study, MACE included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.2
The study’s primary outcome was the time from randomization to the first occurrence of MACE, with a target of 1,225 adjudication-confirmed events. The population was primarily male (71.1%) and predominantly White (68.9%), with a mean age of 66.1 years and a mean diabetes duration of 15.4 years. Participants had an average BMI of 31.3 kg/m² and an HbA1c of 63.5 mmol/mol. At randomization, most patients had coronary artery disease (70.7%), with 42.3% having chronic kidney disease (CKD), 21.1% cerebrovascular disease and 15.7% symptomatic peripheral arterial disease (PAD). Prevalent heart failure was reported in 23% of participants. The majority of participants also had a history of hypertension and were taking at least one antihypertensive medication, with an average blood pressure of 135/77 mmHg. Additionally, approximately 88% of participants were receiving LDL cholesterol-lowering treatments, and their LDL cholesterol levels were generally controlled, ranging from moderate to well.2
These topline results will be followed by the full trial data, which are expected to be presented at a scientific congress in 2025. This presented data may not only add to a growing body of evidence supporting the cardiovascular efficacy of GLP-1 receptor agonists but also highlight the potential of an oral GLP-1RA in achieving these outcomes.
References:
GlobalNewswire. Novo Nordisk A/S: Oral semaglutide demonstrates a 14% reduction in risk of major adverse cardiovascular events in adults with type 2 diabetes in the SOUL trial. 2024. [Press release]. Available at: https://www.globenewswire.com/news-release/2024/10/21/2965998/0/en/Novo-Nordisk-A-S-Oral-semaglutide-demonstrates-a-14-reduction-in-risk-of-major-adverse-cardiovascular-events-in-adults-with-type-2-diabetes-in-the-SOUL-trial.html (accessed 21 October 2024).
McGuire DK, Busui RP, Deanfield J, Inzucchi SE, Mann JFE, Marx N, Mulvagh SL, Poulter N, Engelmann MDM, Hovingh GK, Ripa MS, Gislum M, Brown-Frandsen K, Buse JB. Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial. Diabetes Obes Metab. 2023 Jul;25(7):1932-1941. doi: 10.1111/dom
Disclosure: This article was created by the touchENDOCRINOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
