EFFICACY AND SAFETY OF INJECTABLE INCRETIN THERAPIES IN THE MANAGEMENT OF OBESITY: A SYSTEMATIC REVIEW

Authors

  • Fernanda Rodrigues Lopes Author
  • Travis Ricardo Johnson Author
  • Fabrício Soares Ferreira Author
  • Arthur Alberth Lopes Author
  • Marcos Antônio de Amorim Author
  • Theo Gabriel de Matos Nery Lima Author
  • Giovana Abadia Braga Martins Author
  • Nicolas Ferreira Melo Author
  • Quintiliano Duarte Araujo Author
  • Maria Beatriz Almeida Dario Author
  • Fernando Daniel Pereira Barbosa Author
  • Hygor Henrique Silva Sales Author

DOI:

https://doi.org/10.56238/levv17n60-028

Keywords:

GLP-1 Receptor Agonists, Tirzepatide, Semaglutide, Liraglutide, Obesity, Weight Loss, Systematic Review

Abstract

Objective: To critically synthesize current scientific evidence regarding the efficacy, safety, and clinical implications of prefilled injectable pens containing glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual agonists (GLP-1/GIP) for weight management. Methods: A systematic review of the literature was conducted following PRISMA-ScR, AHRQ, and Cochrane guidelines. Searches were performed in PubMed/MEDLINE, Google Scholar, Embase, Scopus, Web of Science, and ClinicalTrials.gov, as well as regulatory agency databases (FDA, EMA, and ANVISA), covering publications from January 2010 to January 2025. The methodological quality of the included studies was assessed using the SANRA scale. Results: A total of 31 high-quality references were included. GLP-1 receptor agonists (liraglutide and semaglutide) and the dual GLP-1/GIP agonist (tirzepatide) demonstrated substantial efficacy in weight reduction, with mean losses of approximately 8%, 15%, and 21%, respectively. The triple agonist under development, retatrutide, showed promising results, with weight reductions of up to 28%. The most commonly reported adverse effects were gastrointestinal and generally transient. Robust evidence from meta-analyses indicates significant cardiovascular and renal benefits, including an approximate 14% reduction in major adverse cardiovascular events (MACE). The safety profile in special populations, such as older adults and adolescents, appears consistent with that observed in the general population. Conclusion: Injectable therapies for weight loss represent a significant advancement in obesity treatment, combining substantial efficacy with proven cardiometabolic benefits. Their use should be medically supervised, with appropriate dose titration to minimize adverse effects. Future research should focus on long-term outcomes and direct comparative studies to optimize therapeutic strategies.

Downloads

Download data is not yet available.

References

[1] World Health Organization. (2024). Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

[2] Srivastava, G., & Apovian, C. M. (2018). Current pharmacotherapy for obesity. Nature Reviews Endocrinology, 14(1), 12-24. DOI: https://doi.org/10.1038/nrendo.2017.122

[3] Garvey, W. T., Mechanick, J. I., Brett, E. M., et al. (2016). American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocrine Practice, 22(Suppl 3), 1-203. DOI: https://doi.org/10.4158/EP161365.GL

[4] Guo, J., Jou, W., Gavrilova, O., et al. (2023). The GLP-1 receptor agonist PEX-168 reduces body weight in obese mice. Diabetes, 72(Suppl 1), A123.

[5] Tsoukas, M. A., Gogos, A., & Hatzitolios, A. I. (2025). Mechanisms of GLP-1 Receptor Agonist-Induced Weight Loss. The American Journal of Cardiology, 207, 1-10.

[6] Eli Lilly and Company. (2025). Lilly announces positive topline results from Phase 3 TRIUMPH-4 clinical trial of retatrutide. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average

[7] Tricco, A. C., Lillie, E., Zarin, W., et al. (2018). PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Annals of Internal Medicine, 169(7), 467-473. DOI: https://doi.org/10.7326/M18-0850

[8] AHRQ Methods Guide for Effectiveness and Comparative Effectiveness Reviews. (2014). Agency for Healthcare Research and Quality.

[9] Cochrane Handbook for Systematic Reviews of Interventions. (2019). Cochrane.

[10] Novo Nordisk A/S. (2010). Victoza (liraglutide) [prescribing information].

[11] Nauck, M. A., & Meier, J. J. (2018). Incretin hormones: their role in health and disease. Diabetes, Obesity and Metabolism, 20(Suppl 1), 5-21. DOI: https://doi.org/10.1111/dom.13129

[12] Frias, J. P., Davies, M. J., Rosenstock, J., et al. (2024). Tirzepatide versus semaglutide oral and subcutaneous in type 2 diabetes. New England Journal of Medicine, 391(2), 109-121.

[13] Wilding, J. P. H., Batterham, R. L., Calanna, S., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989-1002. DOI: https://doi.org/10.1056/NEJMoa2032183

[14] Garvey, W. T., Batterham, R. L., Bhatta, M., et al. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 28(10), 2066-2075. DOI: https://doi.org/10.1038/s41591-022-02026-4

[15] Pi-Sunyer, X., Astrup, A., Fujioka, K., et al. (2015). A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine, 373(1), 11-22. DOI: https://doi.org/10.1056/NEJMoa1411892

[16] Jastreboff, A. M., Aroda, V. R., Gastaldelli, A., et al. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205-216. DOI: https://doi.org/10.1056/NEJMoa2206038

[17] Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. (2024). JAMA Internal Medicine, 184(2), 175-186. DOI: https://doi.org/10.1001/jamainternmed.2024.2525

[18] Rosenstock, J., Wysham, C., Frías, J. P., et al. (2021). Efficacy and safety of a novel triple hormone receptor agonist tirzepatide in people with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. The Lancet, 398(10295), 143-155. DOI: https://doi.org/10.1016/S0140-6736(21)01324-6

[19] Rosenstock, J., Wysham, C., Frías, J. P., et al. (2023). Triple–Hormone-Receptor Agonist Retatrutide for Obesity. New England Journal of Medicine, 389(6), 557-568.

[20] Drucker, D. J., Buse, J. B., Armstrong, A. W., et al. (2022). Innovation and integration of new therapies for type 2 diabetes in the real world. Diabetes Care, 45(Suppl 2), S211-S220.

[21] Nauck, M. A., Meier, J. J., Mück, T., et al. (2025). Glucagon-like peptide 1 receptor agonists and pancreatitis: a review of the literature. Cleveland Clinic Journal of Medicine, 92(8), 483-495. DOI: https://doi.org/10.3949/ccjm.92a.24113

[22] American Thyroid Association. (2025). Risk of Thyroid Cancer Among GLP1-RA Users. https://www.thyroid.org/risk-thyroid-cancer-glp1-ra-users/

[23] Garg, V., Verma, S., & Connelly, K. (2024). GLP-1 agonists and gastrointestinal adverse events. JAMA, 331(20), 1745-1746. DOI: https://doi.org/10.1001/jama.2024.0049

[24] Sinclair, A. J., Abdelhafiz, A. H., & Rodríguez-Mañas, L. (2015). Diabetes and cardiovascular disease in older people. The Lancet Diabetes & Endocrinology, 3(12), 948-958. DOI: https://doi.org/10.1016/S2213-8587(14)70176-7

[25] Novo Nordisk A/S. (2023). Wegovy (semaglutide) prescribing information for adolescents.

[26] Parker, C. H., Slattery, C., Garg, S. K., et al. (2024). Glucagon-like peptide 1 (GLP-1) receptor agonists’ use during pregnancy: Safety data from regulatory clinical trials. Diabetes, Obesity and Metabolism, 27(8), 4102-4108. DOI: https://doi.org/10.1111/dom.16437

[27] Perkovic, V., Tuttle, K. R., Rossing, P., et al. (2022). Management of patients with diabetes and CKD: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International, 102(5), 974-989. DOI: https://doi.org/10.1016/j.kint.2022.08.012

[28] Cardiovascular and Kidney Outcomes and Mortality With Long-Acting GLP-1 Receptor Agonists. (2025). Diabetes Care, 48(5), 846-856.

[29] Garvey, W. T., Batterham, R. L., Bhatta, M., et al. (2024). Efficacy and safety of once-weekly semaglutide versus daily liraglutide for weight loss in obese adults. Obesity (Silver Spring), 32(1), 1-12.

[30] Schauer, P. R., Bhatt, D. L., Kirwan, J. P., et al. (2017). Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. New England Journal of Medicine, 376(7), 641-651. DOI: https://doi.org/10.1056/NEJMoa1600869

[31] Marso, S. P., Daniels, G. H., Brown-Frandsen, K., et al. (2016). Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine, 375(4):311-322. DOI: https://doi.org/10.1056/NEJMoa1603827

Published

2026-05-14

How to Cite

LOPES, Fernanda Rodrigues et al. EFFICACY AND SAFETY OF INJECTABLE INCRETIN THERAPIES IN THE MANAGEMENT OF OBESITY: A SYSTEMATIC REVIEW. LUMEN ET VIRTUS, [S. l.], v. 17, n. 60, p. e13111, 2026. DOI: 10.56238/levv17n60-028. Disponível em: https://periodicos.newsciencepubl.com/LEV/article/view/13111. Acesso em: 20 may. 2026.