USO DOS AGONISTAS DUPLOS E TRIPLOS DE INCRETINAS (TIRZEPATIDA E RETATRUTIDA) NO TRATAMENTO DA OBESIDADE E DIABETES TIPO 2
DOI:
https://doi.org/10.56238/levv17n59-045Palavras-chave:
Obesidade, Diabetes Mellitus Tipo 2, Tirzepatida, Retatrutida, IncretinasResumo
A obesidade e o diabetes mellitus tipo 2 (DM2) constituem importantes desafios de saúde pública global, demandando abordagens terapêuticas mais eficazes e integradas. Nesse contexto, os agonistas duplos e triplos de incretinas emergem como estratégias inovadoras ao atuarem simultaneamente em múltiplas vias metabólicas. O presente estudo teve como objetivo realizar uma análise crítica e comparativa do uso da tirzepatida e da retatrutida no tratamento da obesidade e do DM2, com base em evidências científicas recentes. Trata-se de uma revisão narrativa de caráter crítico-analítico, conduzida por meio de busca estruturada nas bases PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect e Cochrane Library, contemplando estudos publicados entre 2016 e 2025. Foram incluídos 20 estudos, entre ensaios clínicos, revisões sistemáticas, meta-análises e revisões narrativas. Os resultados indicam que a tirzepatida apresenta eficácia consolidada no controle glicêmico e na redução de peso corporal, enquanto a retatrutida demonstra maior potencial para perda ponderal, possivelmente relacionado ao aumento do gasto energético mediado pela ativação do receptor de glucagon. Entretanto, essa aparente superioridade ocorre em paralelo a maior incidência de eventos adversos e à limitada disponibilidade de evidências de longo prazo. A ausência de estudos comparativos diretos e a heterogeneidade metodológica dificultam a definição do posicionamento ideal dessas terapias. Conclui-se que, embora representem um avanço significativo, os agonistas duplos e triplos de incretinas ainda demandam estudos adicionais, especialmente de longo prazo e com comparação direta, para consolidação de seu papel na prática clínica.
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Referências
BAILEY, C. J.; FLATT, P. R.; CONLON, J. M. Recent advances in peptide-based therapies for obesity and type 2 diabetes. Peptides, v. 173, 2024. DOI: https://doi.org/10.1016/j.peptides.2024.171149.
BAILEY, C. J.; FLATT, P. R.; CONLON, J. M. An update on peptide-based therapies for type 2 diabetes and obesity. Peptides, v. 161, 2023. DOI: https://doi.org/10.1016/j.peptides.2023.170939.
CARUSO, I. et al. Incretin-based therapies for the treatment of obesity-related diseases. npj Metabolic Health and Disease, v. 2, 2024. DOI: https://doi.org/10.1038/s44324-024-00030-5.
FERNANDEZ, C.; LAKSHMI, V.; PAPPACHAN, J. M. Efficacy and safety of incretin co-agonists: transformative advances in cardiometabolic healthcare. World Journal of Cardiology, v. 17, 2025. DOI: https://doi.org/10.4330/wjc.v17.i8.107991.
FIORUCCI, S.; URBANI, G. Tirzepatide for metabolic dysfunction-associated steatohepatitis: results from phase II clinical trials and perspectives. Expert Opinion on Investigational Drugs, v. 34, p. 655–663, 2025. DOI: https://doi.org/10.1080/13543784.2025.2546812.
GALLWITZ, B. Clinical perspectives on the use of the GIP/GLP-1 receptor agonist tirzepatide for the treatment of type 2 diabetes and obesity. Frontiers in Endocrinology, v. 13, 2022. DOI: https://doi.org/10.3389/fendo.2022.1004044.
GOGINENI, P. et al. Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? Expert Opinion on Pharmacotherapy, v. 25, p. 801–818, 2024. DOI: https://doi.org/10.1080/14656566.2024.2356254.
GOLDNEY, J. et al. Triple agonism based therapies for obesity. Current Cardiovascular Risk Reports, v. 19, 2025. DOI: https://doi.org/10.1007/s12170-025-00770-z.
LEMPESIS, I. G.; LIU, J.; DALAMAGA, M. The catcher in the gut: tirzepatide, a dual incretin analog for the treatment of type 2 diabetes mellitus and obesity. Metabolism Open, v. 16, 2022. DOI: https://doi.org/10.1016/j.metop.2022.100220.
LIARAKOS, A. L.; KOLIAKI, C. Novel dual incretin receptor agonists in the spectrum of metabolic diseases with a focus on tirzepatide. Biomedicines, v. 11, 2023. DOI: https://doi.org/10.3390/biomedicines11071875.
MADSBAD, S.; HOLST, J. J. The promise of glucagon-like peptide-1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines. Expert Opinion on Investigational Drugs, v. 34, p. 197–215, 2025. DOI: https://doi.org/10.1080/13543784.2025.2472408.
MELSON, E. et al. What is the pipeline for future medications for obesity? International Journal of Obesity, v. 49, p. 433–451, 2024. DOI: https://doi.org/10.1038/s41366-024-01473-y.
SALHAB, A. et al. Comparative efficacy and safety of tirzepatide vs retatrutide in weight loss: a network meta-analysis of clinical trials. Journal of the Endocrine Society, v. 9, 2025. DOI: https://doi.org/10.1210/jendso/bvaf149.169.
SINHA, B.; GHOSAL, S. Efficacy and safety of GLP-1 receptor agonists, dual agonists, and retatrutide for weight loss in adults with overweight or obesity: a Bayesian network meta-analysis. Obesity, v. 33, p. 2046–2054, 2025. DOI: https://doi.org/10.1002/oby.24360.
SZTANEK, F. et al. New developments in pharmacological treatment of obesity and type 2 diabetes. Biomedicines, v. 12, 2024. DOI: https://doi.org/10.3390/biomedicines12061320.
THIRIVEEDI, M. et al. A narrative review on tirzepatide’s therapeutic potential in glycemic control and cardioprotection. Annals of Medicine & Surgery, 2025. DOI: https://doi.org/10.1097/MS9.0000000000004055.
ULLAH, M.; TAMANNA, S. Obesity: clinical impact, pathophysiology, complications, and modern innovations in therapeutic strategies. Medicines, v. 12, 2025. DOI: https://doi.org/10.3390/medicines12030019.
WINKLER, G. et al. From GLP-1 receptor agonists to triple hormone receptor activation supplemented with glucagon receptor agonism. Orvosi Hetilap, v. 164, p. 1656–1664, 2023. DOI: https://doi.org/10.1556/650.2023.32894.
YAN, K.; YU, H.; BLAISE, B. Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care. Acta Diabetologica, v. 62, p. 1359–1370, 2025. DOI: https://doi.org/10.1007/s00592-025-02534-y.
ZAFFINA, I. et al. Effect of dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist on weight loss in subjects with obesity. Frontiers in Endocrinology, v. 14, 2023. DOI: https://doi.org/10.3389/fendo.2023.1095753.
