Authors: Miodrag Janić, Manfredi Rizzo, Francesco Cosentino, Anca Pantea Stoian, Mojca Lunder, Mišo Šabović & Andrej Janež
Abstract
Introduction
Type 2 diabetes (T2D) management has reached a point where not only optimal glycaemic control is necessary, but also additional interventions with proven cardiovascular risk reduction benefit. Subcutaneous semaglutide has been shown to provide cardiovascular protection, but its use may be limited by its injection formulation. To overcome this limitation, an oral semaglutide tablet has been developed, which could potentially be of the same value as its injection counterpart, but in a much wider group of patients with T2D, thereby allowing for broader cardiovascular risk reduction in this vulnerable patient population.
Methods
A total of 100 consecutive patients with T2D and a disease duration of up to 10 years, without manifest cardiovascular disease, who are treated with metformin (± sulphonylurea) and optimal cardioprotective therapy, will be recruited in a single-blinded, randomized trial named “Semaglutide Anti-atherosclerotic Mechanisms of Action Study (SAMAS).” After 1:1 randomization, patients will receive either oral semaglutide 14 mg daily or placebo for 1 year. The primary outcome comprises changes in atherosclerosis-related structural and functional characteristics of the arterial wall, namely: reduction of the carotid intima-media thickness, improvement of endothelial function and decrease in arterial stiffness. Secondary outcomes are changes in atherogenic small dense low-density lipoproteins, glucose control (HbA1c) and inflammatory markers (hsCRP). Possible correlations between primary endpoints and changes in lipids, HbA1c and high-sensitivity C-reactive protein will be sought.
Discussion
This is the first study to investigate the direct and indirect anti-atherosclerotic mechanisms of oral semaglutide. The results are expected to confirm the position of oral semaglutide in the multifactorial management of T2D with an emphasis on cardiovascular disease prevention.
Trial Registration
ClinicalTrials.gov Identifier: NCT05147896.
Key Summary Points |
Current type 2 diabetes (T2D) management requires additional interventions to achieve proper cardiometabolic benefit. |
Oral semaglutide is the first glucagon-like peptide-1 receptor agonist available on the market, potentially allowing for a significant cardiometabolic risk reduction in a broader population of patients with T2D due to its innovative oral formulation. |
We designed an innovative clinical trial to explore the possible anti-atherosclerotic effects of oral semaglutide, and its effects associated with arterial structure and function parameters in patients with T2D in primary cardiovascular prevention. |
This is the first study to investigate the direct and indirect anti-atherosclerotic mechanisms of oral semaglutide, thus solidating its position in the multifactorial T2D management strategy, with emphasis on cardiovascular disease prevention. |