Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice

<b>Background:</b> Semaglutide, a GLP-1 receptor agonist, has shown promising nephroprotective effects in clinical trials, though real-world data on its long-term impact on renal function in high-risk diabetic nephropathy patients remain scarce. <b>Methods:</b> We conducted a...

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Main Authors: Enrique Luna, Álvaro Álvarez, Jorge Rodriguez-Sabiñón, Juan Villa, Teresa Giraldo, Maria Victoria Martín, Eva Vázquez, Noemi Fernández, Belén Ruiz, Guadalupe Garcia-Pino, Coral Martínez, Lilia Azevedo, Rosa María Diaz, Nicolas Roberto Robles, Guillermo Gervasini
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Language:English
Published: MDPI AG 2025-07-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/7/943
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author Enrique Luna
Álvaro Álvarez
Jorge Rodriguez-Sabiñón
Juan Villa
Teresa Giraldo
Maria Victoria Martín
Eva Vázquez
Noemi Fernández
Belén Ruiz
Guadalupe Garcia-Pino
Coral Martínez
Lilia Azevedo
Rosa María Diaz
Nicolas Roberto Robles
Guillermo Gervasini
author_facet Enrique Luna
Álvaro Álvarez
Jorge Rodriguez-Sabiñón
Juan Villa
Teresa Giraldo
Maria Victoria Martín
Eva Vázquez
Noemi Fernández
Belén Ruiz
Guadalupe Garcia-Pino
Coral Martínez
Lilia Azevedo
Rosa María Diaz
Nicolas Roberto Robles
Guillermo Gervasini
author_sort Enrique Luna
collection DOAJ
description <b>Background:</b> Semaglutide, a GLP-1 receptor agonist, has shown promising nephroprotective effects in clinical trials, though real-world data on its long-term impact on renal function in high-risk diabetic nephropathy patients remain scarce. <b>Methods:</b> We conducted a multicenter, retrospective observational study involving 156 patients with type 2 diabetes and chronic kidney disease (CKD) treated with subcutaneous semaglutide between 2019 and 2023. Inclusion required an eGFR > 15 mL/min/1.73 m<sup>2</sup> or albuminuria > 30 mg/g and at least two years of follow-up. The primary outcome was the change in eGFR slope after semaglutide initiation. Subgroup analyses were performed based on baseline eGFR, albuminuria, and SGLT2i co-treatment. <b>Results:</b> In the whole study population, the median eGFR slope significantly improved from −3.29 (IQR 7.54) to −0.79 (IQR 6.01) mL/min/1.73 m<sup>2</sup>/year post-treatment (<i>p</i> < 0.001). Multiple linear regression showed a hazard ratio for the effect of semaglutide on the eGFR slope of 4.06 (2.43–5.68), <i>p</i> < 0.001. In patients with baseline eGFR < 60 mL/min/1.73 m<sup>2</sup>, the slope improved from −3.77 to −1.01 (<i>p</i> < 0.0001), while patients on concurrent SGLT2i therapy saw slope changes from −2.96 to −0.37 (<i>p</i> < 0.0001). Patients with albuminuria 30–1000 mg/g also improved from −2.96 to −0.04 (<i>p</i> < 0.0001); however, those > 1000 mg/g did not show a significant change (<i>p</i> = 0.184). Semaglutide also reduced BMI (<i>p</i> = 0.04), HbA1c (<i>p</i> = 0.002), triglycerides (<i>p</i> = 0.001), CRP (<i>p</i> = 0.003), and GGT values (<i>p</i> = 0.004). <b>Conclusions:</b> In real-world practice, semaglutide significantly attenuated renal function decline in high-risk diabetic patients, particularly those with advanced CKD or concurrent SGLT2i therapy. These findings support its nephroprotective role beyond glycemic control.
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spelling doaj-art-9da5d47ac36149d19e2f134470d3bafb2025-08-20T03:56:46ZengMDPI AGPharmaceutics1999-49232025-07-0117794310.3390/pharmaceutics17070943Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical PracticeEnrique Luna0Álvaro Álvarez1Jorge Rodriguez-Sabiñón2Juan Villa3Teresa Giraldo4Maria Victoria Martín5Eva Vázquez6Noemi Fernández7Belén Ruiz8Guadalupe Garcia-Pino9Coral Martínez10Lilia Azevedo11Rosa María Diaz12Nicolas Roberto Robles13Guillermo Gervasini14Nephrology Department, Badajoz University Hospital, 06006 Badajoz, SpainDon Benito-Villanueva Hospital, Nephrology Department, 06400 Don Benito, SpainDon Benito-Villanueva Hospital, Nephrology Department, 06400 Don Benito, SpainNephrology Department, Badajoz University Hospital, 06006 Badajoz, SpainNephrology Department, Badajoz University Hospital, 06006 Badajoz, SpainNephrology Department, Badajoz University Hospital, 06006 Badajoz, SpainMérida Hospital, Nephrology Department, 06800 Mérida, SpainMérida Hospital, Nephrology Department, 06800 Mérida, SpainMérida Hospital, Nephrology Department, 06800 Mérida, SpainZafra Hospital, Nephrology Department, 06300 Zafra, SpainZafra Hospital, Nephrology Department, 06300 Zafra, SpainLlerena Hospital, Nephrology Department, 06900 Llerena, SpainLlerena Hospital, Nephrology Department, 06900 Llerena, SpainNephrology Department, Badajoz University Hospital, 06006 Badajoz, SpainInstitute of Molecular Pathology Biomarkers, University of Extremadura, 06006 Badajoz, Spain<b>Background:</b> Semaglutide, a GLP-1 receptor agonist, has shown promising nephroprotective effects in clinical trials, though real-world data on its long-term impact on renal function in high-risk diabetic nephropathy patients remain scarce. <b>Methods:</b> We conducted a multicenter, retrospective observational study involving 156 patients with type 2 diabetes and chronic kidney disease (CKD) treated with subcutaneous semaglutide between 2019 and 2023. Inclusion required an eGFR > 15 mL/min/1.73 m<sup>2</sup> or albuminuria > 30 mg/g and at least two years of follow-up. The primary outcome was the change in eGFR slope after semaglutide initiation. Subgroup analyses were performed based on baseline eGFR, albuminuria, and SGLT2i co-treatment. <b>Results:</b> In the whole study population, the median eGFR slope significantly improved from −3.29 (IQR 7.54) to −0.79 (IQR 6.01) mL/min/1.73 m<sup>2</sup>/year post-treatment (<i>p</i> < 0.001). Multiple linear regression showed a hazard ratio for the effect of semaglutide on the eGFR slope of 4.06 (2.43–5.68), <i>p</i> < 0.001. In patients with baseline eGFR < 60 mL/min/1.73 m<sup>2</sup>, the slope improved from −3.77 to −1.01 (<i>p</i> < 0.0001), while patients on concurrent SGLT2i therapy saw slope changes from −2.96 to −0.37 (<i>p</i> < 0.0001). Patients with albuminuria 30–1000 mg/g also improved from −2.96 to −0.04 (<i>p</i> < 0.0001); however, those > 1000 mg/g did not show a significant change (<i>p</i> = 0.184). Semaglutide also reduced BMI (<i>p</i> = 0.04), HbA1c (<i>p</i> = 0.002), triglycerides (<i>p</i> = 0.001), CRP (<i>p</i> = 0.003), and GGT values (<i>p</i> = 0.004). <b>Conclusions:</b> In real-world practice, semaglutide significantly attenuated renal function decline in high-risk diabetic patients, particularly those with advanced CKD or concurrent SGLT2i therapy. These findings support its nephroprotective role beyond glycemic control.https://www.mdpi.com/1999-4923/17/7/943semaglutidechronic kidney diseasediabetesSGLT2 inhibitorsestimated glomerular filtration rateeGFR slope
spellingShingle Enrique Luna
Álvaro Álvarez
Jorge Rodriguez-Sabiñón
Juan Villa
Teresa Giraldo
Maria Victoria Martín
Eva Vázquez
Noemi Fernández
Belén Ruiz
Guadalupe Garcia-Pino
Coral Martínez
Lilia Azevedo
Rosa María Diaz
Nicolas Roberto Robles
Guillermo Gervasini
Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice
Pharmaceutics
semaglutide
chronic kidney disease
diabetes
SGLT2 inhibitors
estimated glomerular filtration rate
eGFR slope
title Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice
title_full Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice
title_fullStr Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice
title_full_unstemmed Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice
title_short Long-Term Effect of Semaglutide on the Glomerular Filtration Rate Slope in High-Risk Patients with Diabetic Nephropathy: Analysis in Real-World Clinical Practice
title_sort long term effect of semaglutide on the glomerular filtration rate slope in high risk patients with diabetic nephropathy analysis in real world clinical practice
topic semaglutide
chronic kidney disease
diabetes
SGLT2 inhibitors
estimated glomerular filtration rate
eGFR slope
url https://www.mdpi.com/1999-4923/17/7/943
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