Conventional and Stem Cell Therapies for Type 2 Diabetes in Brazil and the United States: A Narrative Review
DOI:
https://doi.org/10.18554/acbiobras.9298Keywords:
Stem Cells, Diabetes Mellitus, Type 2 Diabetes Mellitus, Pharmacological Treatment, Health RegulationAbstract
Introduction: Diabetes mellitus is a chronic disease in which insulin production is low or absent, generating a metabolic imbalance that can compromise several organs. Type 2 diabetes mellitus (T2DM) is the most common type diagnosed in adults and, being largely silent, is often only treated after complications appear. Objective: To describe conventional treatment of T2DM in Brazil and in the United States and the current status of stem cell (SC) therapy, considering evidence, safety, and health regulation. Design: Narrative review of publications from 2000 to 2026 retrieved from PubMed, SciELO, Google Scholar and Consensus, selected by predefined inclusion and exclusion criteria; 30 references were included. Main results: pharmacological treatment remains the therapeutic backbone of T2DM in both Brazil and the United States, with growing regulatory convergence between ANVISA and the FDA regarding newer drug classes; stem cell therapy shows promising results and a favorable safety profile in controlled clinical trials. Conclusion: stem cell therapy remains without regulatory approval for routine use in either country, reinforcing its experimental nature.
References
1. Sociedade Brasileira de Diabetes. Diretrizes da Sociedade Brasileira de Diabetes 2019-2020. São Paulo: SBD; 2019.
2. American Diabetes Association (US). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2010; 33 (Suppl 1): S62-S69. https://doi.org/10.2337/dc10-S062
3. Cerf ME. Beta cell dysfunction and insulin resistance. Frontiers in Endocrinology: Clinical Diabetes (Lausanne). 2013; 4: 37. https://doi.org/10.3389/fendo.2013.00037
4. Andrade LJO, Melo PRS, França LS, Bittencourt AMV. Terapia com células-tronco em diabetes mellitus. Revista de Ciências Médicas e Biológicas. 2012; 11 (1): 79-85. https://api.semanticscholar.org/CorpusID:73883841
5. Guelho D, Paiva I, Cavalheiro M. Diabetes mellitus: um continuum fisiopatológico. Endocrinology Insights. 2013; 8 (1): 44-49. https://doi.org/10.26497/2013.000006.000085
6. Araújo LMB, Brito MMS, Cruz TRP. Tratamento do diabetes mellitus do tipo 2: novas opções. Arquivos Brasileiros de Endocrinologia & Metabologia. 2000; 44 (6): 509-518. https://doi.org/10.1590/S0004-27302000000600011
7. D'Ângelo FA, Leatte PE, Defani MA. O exercício físico como coadjuvante no tratamento do diabetes. Saúde e Pesquisa. 2015; 8 (1): 157-166. http://dx.doi.org/10.17765/1983-1870.2015v8n1p157-166
8. Bertoluci MC, Silva Júnior WS, Valente F, Araujo LR, Lyra R, Castro JJ, Raposo JF, Miranda PAC, Boguszewski CL, Hohl A, Duarte R, Salles JEN, Silva-Nunes J, Dores J, Melo M, Sá JR, Neves JS, Moreira RO, Malachias MVB, Lamounier RN, Malerbi DA, Calliari LE, Cardoso LM, Carvalho MR, Ferreira HJ, Nortadas R, Trujilho FR, Leitão CB, Simões JAR, Reis MIN, Melo P, Marcelino M, Carvalho D. 2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes. Diabetology & Metabolic Syndrome. 2023; 15 (1): 160. https://doi.org/10.1186/s13098-023-01121-x
9. Tran S, Retnakaran R, Zinman B, Kramer CK. Efficacy of glucagon-like peptide-1 receptor agonists compared to dipeptidyl peptidase-4 inhibitors for the management of type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obesity and Metabolism. 2018; 20 (Suppl 1): 68-76. https://doi.org/10.1111/dom.13137
10. Tan X, Liang Y, Rajpura JR, Yedigarova L, Noone J, Xie L, Inzucchi S, de Havenon A. Once-weekly glucagon-like peptide-1 receptor agonists vs dipeptidyl peptidase-4 inhibitors: cardiovascular effects in people with diabetes and cardiovascular disease. Cardiovascular Diabetology. 2023; 22 (1): 319. https://doi.org/10.1186/s12933-023-02051-8
11. Kutz A, Kim DH, Wexler DJ, Liu J, Schneeweiss S, Glynn RJ, Patorno E. Comparative cardiovascular effectiveness and safety of SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors according to frailty in type 2 diabetes. Diabetes Care. 2023; 46 (11): 2004-2014. https://doi.org/10.2337/dc23-0671
12. Nauck MA, D'Alessio DA. Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regarding glycaemic control and body weight reduction. Cardiovascular Diabetology. 2022; 21 (1): 169. https://doi.org/10.1186/s12933-022-01604-7
13. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24 (5): 1294-1301. https://doi.org/10.1634/stemcells.2005-0342
14. Leal AMO, Voltarelli JC. Perspectivas da terapia com células-tronco para o diabetes mellitus tipo 2. Revista Brasileira de Hematologia e Hemoterapia. 2010; 32 (4): 329-334. https://doi.org/10.1590/S1516-84842010005000088
15. Bhansali A, Upreti V, Khandelwal N, Marwaha N, Gupta V, Sachdeva N, Sharma RR, Saluja K, Dutta P, Walia R, Minz R, Bhadada S, Das S, Ramakrishnan S. Efficacy of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cells and Development. 2009; 18 (10): 1407-1416. https://doi.org/10.1089/scd.2009.0164
16. Qi Y, Ma J, Li S, Liu W. Applicability of adipose-derived mesenchymal stem cells in treatment of patients with type 2 diabetes. Stem Cell Res Ther. 2019; 10 (1): 274. https://doi.org/10.1186/s13287-019-1362-2
17. Thompson M, Mei SHJ, Wolfe D, Champagne J, Fergusson D, Stewart DJ, Sullivan KJ, Doxtator E, Lalu M, English SW, Granton J, Hutton B, Marshall J, Maybee A, Walley KR, Santos C, Winston B, McIntyre L. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: an updated systematic review and meta-analysis. EClinicalMedicine. 2020; 19: 100249. https://doi.org/10.1016/j.eclinm.2019.100249
18. Zang L, Li Y, Hao H, Liu J, Cheng Y, Li B, Yin Y, Zhang Q, Gao F, Wang H, Gu S, Li J, Lin F, Zhu Y, Tian G, Chen Y, Gu W, Du J, Chen K, Guo Q, Yang G, Pei Y, Yan W, Wang X, Meng J, Zhang S, Ba J, Lyu Z, Dou J, Han W, Mu Y. Efficacy and safety of umbilical cord-derived mesenchymal stem cells in Chinese adults with type 2 diabetes: a single-center, double-blinded, randomized, placebo-controlled phase II trial. Stem Cell Res Ther. 2022; 13 (1): 180. https://doi.org/10.1186/s13287-022-02848-6
19. Aierken A, Li B, Liu P, Cheng X, Kou Z, Tan N, Zhang M, Yu S, Shen Q, Du X, Enkhbaatar BB, Zhang J, Zhang R, Wu X, Wang R, He X, Li N, Peng S, Jia W, Wang C, Hua J. Melatonin treatment improves human umbilical cord mesenchymal stem cell therapy in a mouse model of type II diabetes mellitus via the PI3K/AKT signaling pathway. Stem Cell Research & Therapy. 2022; 13 (1): 164. https://doi.org/10.1186/s13287-022-02832-0
20. Perico N, Remuzzi G, Griffin MD, Cockwell P, Maxwell AP, Casiraghi F, Rubis N, Peracchi T, Villa A, Todeschini M, Carrara F, Magee BA, Ruggenenti PL, Rota S, Cappelletti L, McInerney V, Griffin TP, Islam MN, Introna M, Pedrini O, Golay J, Finnerty AA, Smythe J, Fibbe WE, Elliman SJ, O'Brien T. Safety and preliminary efficacy of mesenchymal stromal cell (ORBCEL-M) therapy in diabetic kidney disease: a randomized clinical trial (NEPHSTROM). Journal of the American Society of Nephrology. 2023; 34 (10): 1733-1751. https://doi.org/10.1681/ASN.0000000000000189
21. Wu Z, Huang S, Li S, Cai J, Huang L, Wu W, Chen J, Tan J. Bone marrow mesenchymal stem cell and mononuclear cell combination therapy in patients with type 2 diabetes mellitus: a randomized controlled study with 8-year follow-up. Stem Cell Research & Therapy. 2024; 15 (1): 339. https://doi.org/10.1186/s13287-024-03907-w
22. Zeinhom A, Fadallah SA, Mahmoud M. Human mesenchymal stem/stromal cell based-therapy in diabetes mellitus: experimental and clinical perspectives. Stem Cell Research & Therapy. 2024; 15 (1): 384. https://doi.org/10.1186/s13287-024-03974-z
23. Manikandan S, Hariprasad R, Bagepally BS. Efficacy and safety of stem cell therapy in patients with diabetes mellitus: a systematic review and meta-analysis. Systematic Reviews. 2026; 15 (1): 75. https://doi.org/10.1186/s13643-025-03054-0
24. Yamaguchi N, Horio E, Sonoda J, Yamagishi M, Miyakawa S, Murakami F, Hasegawa H, Katahira Y, Mizoguchi I, Fujii Y, Chikazu D, Yoshimoto T. Immortalization of mesenchymal stem cells for application in regenerative medicine and their potential risks of tumorigenesis. International Journal of Molecular Sciences. 2024; 25 (24): 13562. https://doi.org/10.3390/ijms252413562
25. Liang J, Zhang H, Kong W, Deng W, Wang D, Feng X, Zhao C, Hua B, Wang H, Sun L. Safety analysis in patients with autoimmune disease receiving allogeneic mesenchymal stem cells infusion: a long-term retrospective study. Stem Cell Research & Therapy. 2018; 9 (1): 312. https://doi.org/10.1186/s13287-018-1053-4
26. Baranovskii DS, Klabukov ID, Arguchinskaya NV, Yakimova AO, Kisel AA, Yatsenko EM, Ivanov SA, Shegay PV, Kaprin AD. Adverse events, side effects and complications in mesenchymal stromal cell-based therapies. Stem Cell Investigation. 2022; 9: 7. https://doi.org/10.21037/sci-2022-025
27. Agência Nacional de Vigilância Sanitária (Brasil). Resolução da Diretoria Colegiada RDC nº 260, de 21 de dezembro de 2018. Dispõe sobre as regras para a realização de ensaios clínicos com produtos de terapia avançada no Brasil. Diário Oficial da União, Brasília, 26 dez. 2018.
28. Agência Nacional de Vigilância Sanitária (Brasil). Resolução da Diretoria Colegiada RDC nº 338, de 19 de fevereiro de 2020. Dispõe sobre as regras para autorização de terapias avançadas no Brasil. Diário Oficial da União, Brasília, 21 fev. 2020.
29. Agência Nacional de Vigilância Sanitária (Brasil). Resolução da Diretoria Colegiada RDC nº 836, de 13 de dezembro de 2023. Dispõe sobre as boas práticas em células humanas para uso terapêutico e pesquisa clínica. Diário Oficial da União, Brasília, 15 dez. 2023.
30. Brinsfield TN, Pinson NR, Levine AD. The evolution and ongoing challenge of unproven cell-based interventions. Stem Cells Translational Medicine. 2024; 13 (9): 851-858. https://doi.org/10.1093/stcltm/szae050
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Acta Biologica Brasiliensia
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The author(s) retain(s) the rights to the published material. However, publication automatically implies the transfer of copyright, without payment from the journal. The author(s) transfer(s) their economic rights (the right to publish, reproduce, distribute) to the journal. The author(s) do not receive(s) financial remuneration from the Acta Biologica Brasiliensia journal for publishing; the consideration is the dissemination of their work. The author retains authorship (moral rights), but, to publish, transfers or licenses the rights of commercial/economic exploitation (economic rights) to the Acta Biologica Brasiliensia journal, free of charge, making the article open access or, in traditional models, the property of the publisher.
Revistas UFTM