Clinical Impact of Semaglutide Beyond Glycemic Control: A Critical Analysis of Oncogenic Potential and Mitigation of Cardiotoxicity

Introduction: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated unprecedented efficacy in the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, its rapid clinical widespread use has ignited a debate regarding long-term safety, particularly concerning the risk of specific neoplasms and its ability to modulate cardiovascular health, not only as primary prevention but also as a potential agent to mitigate cardiotoxicity. Objectives: This narrative review aims to analyze the most recent evidence from clinical trials and post-marketing surveillance to evaluate the correlation between semaglutide use and the incidence of cancer, as well as the drug’s efficacy in reducing cardiotoxicity induced by anticancer therapies. Results and Discussion: While preclinical rodent models suggested a link to medullary thyroid carcinoma, human epidemiological data remain reassuring, though caution is advised in patients with genetic predisposition. Regarding pancreatic cancer, current meta-analyses do not confirm a significant increase in risk, suggesting that metabolic benefits outweigh potential concerns. Conclusions: Semaglutide is confirmed as a therapeutic tool with a highly favorable benefit–risk profile. While oncological monitoring must continue, the drug’s cardioprotective and anti-inflammatory properties open new frontiers not only in metabolic management but also in safeguarding cardiovascular integrity in complex clinical scenarios.