Liraglutide and Semaglutide Safely Reduce Cardiometabolic Risk in Severe Mental Illness

Patients with severe mental illness (SMI) experience significantly elevated cardiometabolic risk and premature mortality, largely driven by antipsychotic-induced metabolic side effects such as weight gain, insulin resistance, and dyslipidemia. Despite existing guidelines, managing this risk remains a major clinical challenge. Glucagonlike peptide-1 receptor agonists (GLP-1RAs) offer a potential adjunctive therapeutic strategy, given their established benefits in metabolic health. This review evaluates their specific efficacy and safety in SMI patients receiving chronic antipsychotic treatment.

This narrative review conducted a structured search across PubMed/MEDLINE and Cochrane Library, including relevant clinical guidelines. The search focused on randomized controlled trials, systematic reviews, and meta-analyses published between 2015 and 2025 in English or Portuguese. Evidence strength was assessed using the Strength of Recommendation Taxonomy. The review ultimately included 9 studies, comprising 6 randomized controlled trials and 3 evidence synthesis studies, evaluating GLP-1RAs in adults with severe mental illness on chronic antipsychotic treatment.