Semaglutide effects on cardiovascular outcomes in individuals with overweight or obesity who do not have diabetes: a systematic review

<ns3:p>Background: Obesity causes organ dysfunction through several pathophysiological mechanisms, such as the physical impact of increased fat mass, the presence of ectopic fat in tissues and organs, metabolic effects, and inflammatory mechanisms [1]. Prospective studies have shown that fat deposits are associated with cardiovascular outcomes independently of other traditional risk factors. It has been proposed that the prothrombotic and proinflammatory environment of fat deposits has a significant role in the pathogenesis of cardiovascular disease (CVD) [2]. The weight loss induced by anti-obesity drugs may improve cardiovascular risk, and glucagon-like peptide-1 analogs - may promote these benefits independently of weight loss [3]. Glucagon-like peptide-1 receptor agonists (GLP-1Ras), such as semaglutide, have direct effects at multiple sites, including glucose-dependent stimulation of insulin secretion, the suppression of glucagon secretion, appetite reduction, and delayed gastric emptying [2]. Aim of the study: This paper aims to summarize and analyze current knowledge regarding the effects of semaglutide on cardiovascular outcomes in individuals who are overweight or obese but do not have diabetes. Material and methods: This literature review was performed according to PICO guidelines. The MEDLINE database was searched. The following search query was used: “semaglutide and cardiovascular disease”. The “Free full text” filter was applied. Results: Analysis of the SELECT trial showed that in patients with atherosclerotic CVD and who were overweight or obese, treatment with semaglutide 2–4 mg reduced major adverse cardiovascular events and composite heart failure endpoints compared to placebo [4]. In the analysis of the STEP-HFpEF trial, semaglutide was better than placebo in improving heart failure-related symptoms and reducing body weight in obese participants with heart failure-related obesity with preserved ejection fraction [5]. According to the STEP 1 and 4 studies, semaglutide may reduce the use of antihypertensive or lipid-lowering drugs compared with placebo [6]. Conclusions: Semaglutide improves symptoms and physical limitations and reduces inflammation and body weight [7]. Despite the promising results, further research is necessary to assess the long-term effects of semaglutide.</ns3:p>