SEMAGLUTIDA E O RISCO CARDIOVASCULAR NA OBESIDADE: A RELAÇÃO CRÍTICA ENTRE TOLERABILIDADE, ADESÃO E A SUSTENTAÇÃO DO BENEFÍCIO CLÍNICO

Introduction: Obesity is a chronic disease with a high global prevalence and is intrinsically linked to the development of cardiovascular diseases. Although lifestyle interventions are the foundation of treatment, maintaining long-term weight loss remains challenging, making adjunctive pharmacotherapy necessary. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) analog, has been shown to induce robust body weight loss, with an average reduction of up to 16.0% in phase III clinical trials. However, the magnitude and mechanism of its impact on subclinical cardiometabolic risk markers in patients with obesity still require consolidation. The present study evaluated the impact of semaglutide therapy on cardiovascular risk markers and subclinical cardiometabolic outcomes in individuals with obesity, with or without type 2 diabetes. Methodology: A meta- analysis review was conducted, with the search performed in the electronic database PubMed. The search was delimited to the last 5 years and restricted to Randomized Controlled Trials (RCTs), Systematic Reviews, and Meta-Analyses. Following screening, a total of 12 articles were deemed eligible. Results: The primary evidence demonstrated that semaglutide 2.4 mg per week conferred a relevant significant reduction in the risk of Major Adverse Cardiovascular Events (MACE) of up to 20% in individuals with overweight/obesity and established cardiovascular disease, independent of glycemic control. Semaglutide also demonstrated consistent benefits in metabolic and inflammatory markers, being associated with a significant reduction in C-Reactive Protein (CRP) and an improvement in lipid profiles (including LDL-C and triglycerides). The mechanism of action is attributed to appetite suppression and multiple direct actions on the vascular system, such as its anti-inflammatory effect. Discussion: Semaglutide is positioned as a superior therapy in the management of obesity and cardiovascular risk, being particularly effective in combating inflammation and dyslipidemia. However, the realization of long-term cardiometabolic benefits critically depends on sustained adherence to treatment. The main clinical limitation lies in tolerability, as the high incidence of gastrointestinal adverse events is a factor that leads to discontinuation, which nullifies cardiovascular protection. Conclusion: Semaglutide is an important tool that redefines the approach to obesity toward integrated cardiometabolic risk management. Future studies are suggested to focus on the evaluation and standardization of direct vascular biomarkers.