IMPACT OF INCRETIN AGONISTS ON CARDIAC REMODELING AND RENAL PROTECTION IN NON-DIABETIC PATIENTS
Abstract
The development of incretin agonists has been considered a significant advancement in contemporary pharmacology, with evidence suggesting an action beyond glycemic control, possibly mediated by the modulation of inflammatory pathways and oxidative stress. This integrative review analyzes the impact of these therapies on cardiac remodeling and renal protection in non-diabetic populations. Methodology: it was based on the analysis of evidence from the last five years extracted from the PUBMED/MEDLINE, LILACS and SCIELO databases, using the PICO strategy to select studies on cardiorenal outcomes. Results: GLP-1 agonists and co-agonists appear to act pleiotropically, promoting a reduction in ventricular mass, mitigation of volume overload, and preservation of the glomerular filtration rate. Inhibition of the NHE3 exchanger and direct protection of podocytes were observed, resulting in a reduction in albuminuria and interstitial fibrosis. Conclusion: the administration of these compounds offers a promising strategy for cardiac and renal protection, although precision medicine and monitoring of gastrointestinal tolerability are essential for their clinical applicability in non-diabetic patients.
Author Biographies
Physician. Medical Residency in Internal Medicine. Medical Residency in Intensive Care Medicine. Specialist in Medical Care. Postgraduate student in Nutrology.
Graduated in Medicine.
Graduated in Nutrition. Specialization in Nutrition in Nephrology.
Undergraduate Medical Student.
Undergraduate Medical Student.
Undergraduate Medical Student.
Undergraduate Medical Student.
Undergraduate Medical Student.
Graduated in Nutrition.
Master’s Degree in Engineering and Environmental Sciences.
References
BLAHA, M. J. et al. All-cause and cause-specific mortality in individuals with zero or minimal coronary artery calcium. Atherosclerosis, v. 294, p. 72-79, 2019.
BORLAUG, B. A. et al. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nature Medicine, v. 31, n. 2, p. 544-551, fev. 2025.
BROCKMEYER, M. et al. Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data. Journal of Nephrology, v. 37, n. 2, p. 309-321, 2024.
GALLI, M. et al. Cardiovascular effects and tolerability of GLP-1 receptor agonists: a systematic review and meta-analysis of 99,599 patients. Journal of the American College of Cardiology, v. 86, n. 20, p. 1805–1819, nov. 2025.
GUO, H. et al. Glucagon-like peptide-1 analog prevents obesity-related glomerulopathy by inhibiting autophagy overactivation in podocytes. American Journal of Physiology-Renal Physiology, v. 314, n. 2, p. F181-F189, 2018.
HEERSPINK, H. J. L. et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes: the FLOW trial. The New England Journal of Medicine, v. 391, n. 2, p. 109-121, 2024.
HERNANDEZ, A. F. et al. Albiglutide and cardiovascular outcomes (Harmony Outcomes). The Lancet, v. 392, n. 10157, p. 1519-1529, 2018.
KOSIBOROD, M. N. et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. The New England Journal of Medicine, v. 389, n. 12, p. 1069-1084, 2023.
LINCOFF, A. M. et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. The New England Journal of Medicine, v. 389, n. 24, p. 2221-2232, 2023.
NAUCK, M. A.; MEIER, J. J. Incretin-based therapies: challenges, hopes, and promised successes. The Lancet Diabetes & Endocrinology, v. 9, n. 8, p. 525-544, 2021.
NDUMELE, C. E. et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation, v. 148, n. 20, p. 1606-1635, 2023.
NEAL, B. et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England Journal of Medicine, v. 377, n. 7, p. 644-657, 2017.
PACKER, M. et al. Interaction of Chronic Kidney Disease and the Effects of Tirzepatide (SUMMIT Trial). Journal of the American College of Cardiology, v. 85, n. 18, p. 1721–1735, maio 2025.
PERKOVIC, V. et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. The New England Journal of Medicine, v. 380, n. 24, p. 2295-2306, 2019.
RAZAVI, A. C. et al. Allocation of Semaglutide According to Coronary Artery Calcium and BMI: Applying the SELECT Trial to MESA. Journal of the American College of Cardiology Cardiovasc Imaging, v. 18, n. 4, p. 451-461, abr. 2025.
SIDDIQUI, H. F. et al. Sex differences in the efficacy of GLP-1 receptor agonists. Diabetes, Obesity and Metabolism, v. 27, n. 12, p. 6847-6856, dez. 2025.
SMOLDEREN, K. G. et al. Lower risk of cardiovascular events in patients initiated on semaglutide 2.4 mg in the real-world: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World). Diabetes, Obesity and Metabolism, v. 27, n. 11, p. 6691-6704, nov. 2025.
SRIDHAR, V. S. et al. Making a case for the combined use of SGLT2 inhibitors and GLP1 receptor agonists for cardiorenal protection. Brazilian Journal of Nephrology, v. 42, n. 4, p. 467-477, 2020.
WIBERG, S. et al. Efficacy of a glucagon-like peptide-1 agonist and restrictive versus liberal oxygen supply in patients undergoing coronary artery bypass grafting or aortic valve replacement: study protocol for a 2-by-2 factorial designed, randomised clinical trial. British Medical Journal Open, v. 11, n. 11, p. e052340, 2021.
License
Copyright (c) 2026 RECIMA21 - Revista Científica Multidisciplinar - ISSN 2675-6218
This work is licensed under a Creative Commons Attribution 4.0 International License.
Os direitos autorais dos artigos/resenhas/TCCs publicados pertecem à revista RECIMA21, e seguem o padrão Creative Commons (CC BY 4.0), permitindo a cópia ou reprodução, desde que cite a fonte e respeite os direitos dos autores e contenham menção aos mesmos nos créditos. Toda e qualquer obra publicada na revista, seu conteúdo é de responsabilidade dos autores, cabendo a RECIMA21 apenas ser o veículo de divulgação, seguindo os padrões nacionais e internacionais de publicação.