Renal Outcomes of GLP-1 and Dual GIP/GLP-1 Agonists: A New Frontier in Nephrology
DOI:
https://doi.org/10.63969/xgt2jm52Keywords:
GLP-1 receptor agonists, GIP/GLP-1 receptor agonists, diabetic kidney disease, tirzepatide, renal outcomes, eGFR, albuminuria, inflammation, oxidative stressAbstract
Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) worldwide, and incretin-based therapies have emerged as potential tools for organ protection beyond glucose control. This multicenter prospective study compared renal, metabolic, and cardiovascular outcomes in adults with type 2 diabetes mellitus (T2DM) treated with GLP-1 receptor agonists (GLP-1 RAs) or dual GIP/GLP-1 receptor agonists (GIP/GLP-1 RAs) across Mexico, Colombia, and Ecuador between 2023 and 2024. A total of 512 patients (298 GLP-1 RA, 214 GIP/GLP-1 RA) were followed for 12 months. Dual GIP/GLP-1 therapy showed a significantly smaller annual eGFR decline (−0.6 vs. −1.5 mL/min/1.73 m²; p=0.001) and greater albuminuria reduction (−27.4% vs. −19.0%; p=0.02), with more participants achieving ≥30% UACR reduction (43.9% vs. 34.2%; p=0.04). Improvements in HbA1c (−1.8% vs. −1.2%), body weight (−9.1 vs. −6.4 kg), and systolic blood pressure (−8.4 vs. −6.8 mmHg) were also greater with dual therapy (all p<0.05). Inflammatory and oxidative stress markers decreased more significantly in the GIP/GLP-1 group (IL-6 −34.8%, CRP −42%, MDA −1.4 μmol/L; all p<0.02). Major renal events (CKD stage ≥4 or ≥40% eGFR decline) and cardiovascular outcomes (heart failure hospitalization, myocardial infarction, cardiovascular death) were less frequent with dual agonists, translating to a 28% relative risk reduction in composite cardiorenal events (HR 0.72; 95% CI 0.54–0.96; p=0.02). These findings demonstrate that dual GIP/GLP-1 receptor agonists provide superior renal preservation, metabolic optimization, and cardiorenal protection compared with GLP-1 RAs alone, supporting their integration into early DKD management.
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Copyright (c) 2025 Martín Gomez-Lujan, Melina Lucia Pineda Aguilar , José Enrique González Araujo, Daniela María Fernández Lugo, Iván Alfonso Velasco Pomader, María José Gavino Pineda , Javier Alberto Soto Castillo, Andrés Marcelo Córdova López (Autor/a)
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