Physician-authored summaries and commentary on the most important medical research, provided by the NEJM Group, a division of the Massachusetts Medical Society.
© Massachusetts Medical SocietyMay 2025
The oral version lowered the incidence of adverse CV events by two percentage points during four years.
Randomised trials have shown that injected semaglutide lowers risk for adverse cardiovascular events in patients with type 2 diabetes (NEJM JW Gen Med 1 Jul 2024 and N Engl J Med 2024; 391: 109-121; NEJM JW Cardiol Nov 2016 and N Engl J Med 2016; 375: 1834-1844). To find out if the oral version confers similar benefit, researchers conducted an industry-sponsored randomised trial that involved nearly 10,000 patients with type 2 diabetes.
Enrolment criteria included age 50 years or older and history of atherosclerotic cardiovascular (CV) disease or chronic kidney disease; most patients (about 84%) qualified with the CV criterion. At baseline, mean body mass index was 31 kg/m2, mean glycated haemoglobin (HbA1c) was 64 mmol/mol (8%) and median diabetes duration was 15 years. Participants received oral semaglutide (titrated to 14 mg daily if tolerated) or placebo.
During mean follow up of four years, incidence of the primary outcome (CV-related death, myocardial infarction [MI] or stroke) was significantly lower with semaglutide than with placebo (12% vs 13.8%); nonfatal MI accounted for most of this difference. Overall mortality was 10.9% with semaglutide and 12.0% with placebo. Semaglutide recipients lost more weight than placebo recipients (means, −4 kg vs −1 kg); mean HbA1c was between one-half and one percentage point lower in the semaglutide group throughout the trial.
Comment: We now have evidence that oral semaglutide improves CV outcomes in patients with type 2 diabetes and known CV disease. The difference of about two percentage points during several years is similar to the difference seen with injected semaglutide or liraglutide. When the main purpose of starting a glucagon-like peptide-1 (GLP-1)-receptor agonist is to lower CV risk in patients like those in this trial, we now have the option of oral or injected therapy. However, cost is a potential barrier – the cash price without insurance coverage is about US$1000 (about A$1600) monthly.
Allan S. Brett, MD, Clinical Professor of Medicine, University of Colorado School of Medicine, Aurora, USA.
McGuire DK, et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med 2025 Mar 29; e-pub (https://doi.org/10.1056/ NEJMoa2501006).
This summary is taken from the following Journal Watch titles: General Medicine, Cardiology, Ambulatory Medicine.