COMPARISON BETWEEN SEMAGLUTIDE, TIRZEPATIDE, AND NOVEL TRIPLE AGONISTS: EFFICACY, SAFETY, AND CLINICAL IMPLICATIONS
DOI:
https://doi.org/10.36557/2674-9432.2026v5n3p3036-3048Palavras-chave:
obesity; semaglutide; tirzepatide; retatrutide; incretin agonists.Resumo
Obesity is a chronic, multifactorial, and relapsing condition associated with increased cardiometabolic, inflammatory, cardiovascular, renal, and functional risk. In recent years, incretin-based therapies have profoundly transformed the pharmacological treatment of obesity, particularly following the introduction of semaglutide 2.4 mg, tirzepatide, and, more recently, investigational triple agonists such as retatrutide. This narrative review aimed to compare the efficacy, safety, and clinical implications of semaglutide, tirzepatide, and novel triple agonists in the management of obesity and its comorbidities. The analysis was based on clinical trials, follow-up studies, and reviews published between 2019 and 2026, organized according to the PICo strategy. The findings indicate that semaglutide provides robust and sustained weight reduction, with additional evidence of cardiovascular benefit in individuals with overweight or obesity and established cardiovascular disease. Tirzepatide, in turn, demonstrated greater weight reduction in clinical trials and in direct comparison with semaglutide, in addition to marked metabolic effects. Retatrutide, a triple agonist targeting GIP, GLP-1, and glucagon receptors, showed promising results in a phase 2 trial, although it still requires confirmation in phase 3 studies and regulatory evaluation. These therapies represent a paradigm shift in obesity treatment, demanding long-term follow-up, individualized therapeutic planning, and careful monitoring regarding safety, adherence, access, and clinical sustainability.
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Copyright (c) 2026 Hugo Calesso dos Reis, Rodolfo de Oliveira Medeiros, Cristiano Machado Galhardi, Nathalia Miranda Garcia Santinelli, Julia Martinez Zochio, Helena Dantas Oliveira, Bianca Paxiega Bandeira, Letícia Borges Braos, Maria Laura Freitas Nogueira, Gabriele dos Santos Oliveira, Ana Cecília Andrade Fernandes, Maria Eduarda Buratti Gomes
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