Novas abordagens terapêuticas para o uso dos agonistas de GLP-1 além do tratamento do diabetes
DOI:
https://doi.org/10.11606/issn.1679-9836.v105i3e-226930Palavras-chave:
Fármacos Cardiovasculares, Fármacos Neuroprotetores, Doença Crônica, Obesidade, IncretinasResumo
As principais indicações para o uso dos agonistas do receptor de GLP-1 referem-se ao controle da obesidade e a pacientes diabéticos, no entanto, seu uso tem sido sugerido em novas abordagens terapêuticas. O estudo objetiva elencar as vantagens clínicas do uso de agonistas do GLP-1 no tratamento do diabetes mellitus e identificar novas implicações terapêuticas em outras doenças crônicas. Trata-se de uma revisão narrativa da literatura, realizada por meio de levantamento bibliográfico nas bases de dados MEDLINE® via PubMed®. De acordo com os critérios de elegibilidade, foram selecionados 28 artigos. Constatou-se que os benefícios dos agonistas do GLP-1 vão além do controle glicêmico. O fármaco proporciona perda de peso substancial com baixo risco de hipoglicemia. A terapia demonstrou impactos pleiotrópicos sistêmicos, consolidando ações de cardioproteção e nefroproteção que reduzem eventos cardiovasculares adversos e retardam a progressão da doença renal. A literatura também apontou potencial anti-inflamatório, melhora de marcadores de esteatose hepática e efeitos neuroprotetores promissores contra as doenças de Alzheimer e Parkinson. Conclui-se que a prática médica passa por uma mudança de paradigma, na qual esses fármacos atuam como modificadores do risco cardiometabólico e multissistêmico. Enquanto as evidências para obesidade e desfechos cardiorrenais são sólidas, a prescrição direcionada a quadros hepáticos e neurodegenerativos ainda requer cautela e ensaios clínicos específicos.
Downloads
Referências
1. Roglic G. WHO Global report on diabetes: A summary. Int J Noncommun Dis. 2016;1(1):3-8. Doi: 10.4103/2468-8827.184853
2. Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The Growing Epidemic of Diabetes Mellitus. Curr Vasc Pharmacol. 2020;18(2):104-9. Doi: 10.2174/1570161117666190405165911
3. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. Doi: 10.1016/j.diabres.2021.109119
4. Collaborators GBDD. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402(10397):203-34. Doi: 10.1016/S0140-6736(23)01301-6
5. International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium: 2021. https://www.diabetesatlas.org.
6. Aroda VR. A review of GLP-1 receptor agonists: Evolution and advancement, through the lens of randomised controlled trials. Diabetes Obes Metab. 2018;20 Suppl 1:22-33. Doi: 10.1111/dom.13162
7. Janzen KM, Steuber TD, Nisly SA. GLP-1 Agonists in Type 1 Diabetes Mellitus. Ann Pharmacother. 2016;50(8):656-65. Doi: 10.1177/1060028016651279
8. Maselli DB, Camilleri M. Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity. Adv Exp Med Biol. 2021;1307:171-92. Doi: 10.1007/5584_2020_496
9. Muller TD, Finan B, Bloom SR, D'Alessio D, Drucker DJ, Flatt PR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72-130. Doi: 10.1016/j.molmet.2019.09.010
10. Prattichizzo F, de Candia P, Ceriello A. Diabetes and kidney disease: emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists. Metabolism. 2021;120:154799. Doi: 10.1016/j.metabol.2021.154799
11. Yaribeygi H, Rashidy-Pour A, Atkin SL, Jamialahmadi T, Sahebkar A. GLP-1 mimetics and cognition. Life Sci. 2021;264:118645. Doi: 10.1016/j.lfs.2020.11864
12. Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2021;46:101102. Doi: 10.1016/j.molmet.2020.101102
13. Bendotti G, Montefusco L, Lunati ME, Usuelli V, Pastore I, Lazzaroni E, et al. The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists. Pharmacol Res. 2022;182:106320. Doi: 10.1016/j.phrs.2022.106320
14. Xu D, Nair A, Sigston C, Ho C, Li J, Yang D, et al. Potential Roles of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs) in Nondiabetic Populations. Cardiovasc Ther. 2022;2022:6820377. Doi: 10.1155/2022/6820377
15. Boer GA, Holst JJ. Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches. Biology (Basel). 2020;9(12). Doi: 10.3390/biology9120473
16. Cesaro A, De Michele G, Fimiani F, Acerbo V, Scherillo G, Signore G, et al. Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options. Front Cardiovasc Med. 2023;10:1187735. Doi: 10.3389/fcvm.2023.1187735
17. Elbert A, Castellaro C, Litwak L, Inserra F, Wassermann A, Sinay I. Renal effects of GLP-1 agonists in type 2 diabetes. Medicina (B Aires). 2022;82(4):576-90
18. Galindo RJ, Dhatariya K, Gomez-Peralta F, Umpierrez GE. Safety and Efficacy of Inpatient Diabetes Management with Non-insulin Agents: an Overview of International Practices. Curr Diab Rep. 2022;22(6):237-46. Doi: 10.1007/s11892-022-01464-1
19. Garg V, Verma S, Connelly K. Mechanistic insights regarding the role of SGLT2 inhibitors and GLP1 agonist drugs on cardiovascular disease in diabetes. Prog Cardiovasc Dis. 2019;62(4):349-57. Doi: 10.1016/j.pcad.2019.07.005
20. Grenet G, Ribault S, Nguyen GB, Glais F, Metge A, Linet T, et al. GLUcose Control Safety & Efficacy in type 2 DIabetes, a systematic review and NETwork meta-analysis. PLoS One. 2019;14(6):e0217701. Doi: 10.1371/journal.pone.0217701
21. Kılıçkap M, Kayıkçıoğlu M, Tokgözoğlu L. An updated perspective and pooled analysis of cardiovascular outcome trials of GLP-1 receptor agonists and SGLT-2 inhibitors. Anatol J Cardiol. 2021;25(2):61-76. Doi: 10.14744/AnatolJCardiol.2020.06630
22. Laurindo LF, Barbalho SM, Guiguer EL, Souza MSS, Souza GA, Fidalgo TM, et al. GLP-1a: Going beyond Traditional Use. Int J Mol Sci. 2022;23(2). Doi: 10.3390/ijms23020739
23. Lee YM, Lee SH, Kim TH, Park EJ, Park YA, Jang JS. Cardiovascular outcomes with glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: A meta-analysis. Cardiol J. 2022;29(3):499-508. Doi: 10.5603/CJ.a2020.0140
24. Li J, Ji C, Zhang W, Lan L, Ge W. Effect of new glucose-lowering drugs on stroke in patients with type 2 diabetes: A systematic review and Meta-analysis. J Diabetes Complications. 2023;37(1):108362. Doi: 10.1016/j.jdiacomp.2022.108362
25. Martins EB, Lima EG, Pitta FG, Carvalho LNS, Queiroz TD, Serrano Junior CV. Pharmacological therapy and cardiovascular risk reduction for type 2 diabetes. Rev Assoc Med Bras. 2020;66(9):1283-8. Doi: 10.1590/1806-9282.66.9.1283
26. Mehdi SF, Pusapati S, Anwar MS, Lohana D, Kumar P, Nandula SA, et al. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front Immunol. 2023;14:1148209. Doi: 10.3389/fimmu.2023.1148209
27. Rolek B, Haber M, Gajewska M, Rogula S, Pietrasik A, Gasecka A. SGLT2 Inhibitors vs. GLP-1 Agonists to Treat the Heart, the Kidneys and the Brain. J Cardiovasc Dev Dis. 2023;10(8). Doi: 10.3390/jcdd10080322
28. Sheahan KH, Wahlberg EA, Gilbert MP. An overview of GLP-1 agonists and recent cardiovascular outcomes trials. Postgrad Med J. 2020;96(1133):156-61. Doi: 10.1136/postgradmedj-2019-137186
29. Gorriz JL, Romera I, Cobo A, O'Brien PD, Merino-Torres JF. Glucagon-Like Peptide-1 Receptor Agonist Use in People Living with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Narrative Review of the Key Evidence with Practical Considerations. Diabetes Ther. 2022;13(3):389-421. Doi: 10.1007/s13300-021-01198-5
30. Guo M, Gu J, Teng F, Chen J, Ma X, Chen Q, et al. The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis. Endocrine. 2020;67(2):294-304. Doi: 10.1007/s12020-019-02175-6
31. Del Prato S, Gallwitz B, Holst JJ, Meier JJ. The incretin/glucagon system as a target for pharmacotherapy of obesity. Obes Rev. 2022;23(2):e13372. Doi: 10.1111/obr.13372
32. Cornell S. A review of GLP-1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once-weekly agents. J Clin Pharm Ther. 2020;45 Suppl 1(Suppl 1):17-27. Doi: 10.1111/jcpt.13230
33. Reich N, Holscher C. The neuroprotective effects of glucagon-like peptide 1 in Alzheimer's and Parkinson's disease: An in-depth review. Front Neurosci. 2022;16:970925. Doi: 10.3389/fnins.2022.970925
34. Ma X, Liu Z, Ilyas I, Little PJ, Kamato D, Sahebka A, et al. GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential. Int J Biol Sci. 2021;17(8):2050-68. Doi: 10.7150/ijbs.59965
35. Sloan LA. Review of glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects. J Diabetes. 2019;11(12):938-48. Doi: 10.1111/1753-0407.12969
36. Gentilella R, Pechtner V, Corcos A, Consoli A. Glucagon-like peptide-1 receptor agonists in type 2 diabetes treatment: are they all the same? Diabetes Metab Res Rev. 2019;35(1):e3070. Doi: 10.1002/dmrr.3070
37. Nevola R, Epifani R, Imbriani S, Tortorella G, Aprea C, Galiero R, et al. GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives. Int J Mol Sci. 2023;24(2). Doi: 10.3390/ijms24021703
38. Bihan H, Ng WL, Magliano DJ, Shaw JE. Predictors of efficacy of GLP-1 agonists and DPP-4 inhibitors: A systematic review. Diabetes Res Clin Pract. 2016;121:27-34. Doi: 10.1016/j.diabres.2016.08.011
39. Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017;19(4):524-36. Doi: 10.1111/dom.12849
40. Gilbert MP, Pratley RE. GLP-1 Analogs and DPP-4 Inhibitors in Type 2 Diabetes Therapy: Review of Head-to-Head Clinical Trials. Front Endocrinol (Lausanne). 2020;11:178. Doi: 10.3389/fendo.2020.00178
41. Sharma D, Verma S, Vaidya S, Kalia K, Tiwari V. Recent updates on GLP-1 agonists: Current advancements & challenges. Biomed Pharmacother. 2018;108:952-62. Doi: 10.1016/j.biopha.2018.08.088
42. Brown E, Cuthbertson DJ, Wilding JP. Newer GLP-1 receptor agonists and obesity-diabetes. Peptides. 2018;100:61-7. Doi: 10.1016/j.peptides.2017.12.009
43. Parker VER, Robertson D, Wang T, Hornigold DC, Petrone M, Cooper AT, et al. Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist. J Clin Endocrinol Metab. 2020;105(3). Doi: 10.1210/clinem/dgz047
44. Davies MJ, Bergenstal R, Bode B, Kushner RF, Lewin A, Skjøth TV, et al. Efficacy of Liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA. 2015;314:687-99. Doi: 10.1001/jama.2015.9676.
45. Boyle JG, Livingstone R, Petrie JR. Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review. Clin Sci (Lond). 2018;132(15):1699-709. Doi: 10.1042/CS20171299
46. Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Kober LV, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med. 2015;373(23):2247-57. Doi: 10.1056/NEJMoa1509225
47. Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, et al. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2017;377(13):1228-39. Doi: 10.1056/NEJMoa1612917
48. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311-22. Doi: 10.1056/NEJMoa1603827
49. Orabi B, Kaddoura R, Omar AS, Carr C, Alkhulaifi A. Molecular and clinical roles of incretin-based drugs in patients with heart failure. Heart Fail Rev. 2018;23(3):363-76. Doi: 10.1007/s10741-018-9702-3
50. Sarafidis P, Ferro CJ, Morales E, Ortiz A, Malyszko J, Hojs R, et al. SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease. A consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA. Nephrol Dial Transplant. 2020;35(10):1825. Doi: 10.1093/ndt/gfz137
51. Cehic MG, Nundall N, Greenfield JR, Macdonald PS. Management Strategies for Posttransplant Diabetes Mellitus after Heart Transplantation: A Review. J Transplant. 2018;2018:1025893. Doi: 10.1155/2018/1025893
52. Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018;27(4):740-56. Doi: 10.1016/j.cmet.2018.03.001
53. Burgmaier M, Liberman A, Mollmann J, Kahles F, Reith S, Lebherz C, et al. Glucagon-like peptide-1 (GLP-1) and its split products GLP-1(9-37) and GLP-1(28-37) stabilize atherosclerotic lesions in apoe(-)/(-) mice. Atherosclerosis. 2013;231(2):427-35. Doi: 10.1016/j.atherosclerosis.2013.08.033
54. Kuroki T, Tanaka R, Shimada Y, Yamashiro K, Ueno Y, Shimura H, et al. Exendin-4 Inhibits Matrix Metalloproteinase-9 Activation and Reduces Infarct Growth After Focal Cerebral Ischemia in Hyperglycemic Mice. Stroke. 2016;47(5):1328-35. Doi: 10.1161/STROKEAHA.116.012934
55. Newsome PN, Ambery P. Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver. J Hepatol. 2023;79(6):1557-65. Doi: 10.1016/j.jhep.2023.07.033
Downloads
Publicado
Edição
Seção
Licença
Direitos autorais (c) 2026 Egídio Bezerra da Silva Neto, Bruno Rocha de Souza Silva, Guilherme Lages Matias, Hugo Natan de Sá Novaes Pereira, Marcio Vinicius Ferreira Sales, David Fernandes Lima, Carlos Alberto de Lima Botelho Filho, Matheus Rodrigues Lopes
Este trabalho está licenciado sob uma licença Creative Commons Attribution-ShareAlike 4.0 International License.
