Semaglutide Combined with Physical Training: Impact on Diabetic Kidney Disease Morbidity

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Semaglutide Combined with Physical Training: Impact on Diabetic Kidney Disease Morbidity

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Co-author 1

Eloiza de Oliveira Silva eloizaosilva@usp.br University of Sao Paulo and Faculty of Medical Sciences of Santa Casa de Sao Paulo Nursing Sao Paulo Brazil *

Co-author 2

Jessica Paola Garcia Villalba jessica.garcia08@usp.br University of Sao Paulo Nursing Rio de Janeiro Brazil -

Co-author 3

Maikol Lucas de Camargo Gonçalves maikollcg@gmail.com University of Sao Paulo Nursing Sao Paulo Brazil -

Co-author 4

Juliana Veloso Gusmão juliana.veloso.silva@usp.br University of Sao Paulo Nursing Sao Paulo Brazil -

Co-author 5

Carla Djamila de Pina Victoria carlavictoria2001@usp.br University of Sao Paulo Nursing Sao Paulo Brazil -

Co-author 6

Fernanda Borges fernanda.teixeiraborges@gmail.com Federal University of Sao Paulo Nephrology Sao Paulo Brazil -

Co-author 7

Maria de Fatima Fernandes Vattimo nephron@usp.br University of Sao Paulo Nursing Sao Paulo Brazil -

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

Diabetic kidney disease (DKD) is one of the most common complications of type 2 diabetes mellitus (T2DM) and a leading cause of renal replacement therapy. This study investigated the renoprotective effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), semaglutide, combined with moderate physical training (PT), using both in vivo and in vitro approaches.

Methods

Male wistar rats allocated into six groups: control, GLP-1RA, T2DM, T2DM+PT, T2DM+GLP-1RA and T2DM+PT+GLP-1RA. Interventions lasted 28 days. Renal function (inulin clearance, serum creatinine, microalbuminuria), renal hemodynamics, oxidative biomarkers (urinary peroxides, lipid peroxidation, nitrates, tissue thiols, catalase), and mitochondrial enzyme activity (citrate synthase) were evaluated. In parallel, HK-2 cells were cultured under normal glucose (5.5 mM) or high glucose (30 mM) conditions and treated with semaglutide (400 nM) for up to 48 hours. Cell viability was assessed using MTT assay.

Results

The combination of semaglutide and PT in diabetic rats significantly improved glomerular filtration rate, reduced serum creatinine, microalbuminuria, renal oxidative stress, and vascular resistance, while enhancing renal blood flow and citrate synthase activity. In vitro, semaglutide attenuated high-glucose-induced cytotoxicity in HK-2 cells, preserving cellular viability.

Conclusion

Combined treatment with semaglutide and moderate physical training attenuated the progression of DKD induced by T2DM. These findings reinforce the superior renoprotective effects of the combined therapy compared to isolated interventions, particularly through improved renal hemodynamics and reduced oxidative stress. Overall, the data highlight the therapeutic potential of this strategy in mitigating DKD progression

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