Renal Outcomes of GLP-1 Receptor Agonists and Tirzepatide Across CKD Stages and Metabolic Phenotypes (Type 2 Diabetes and/or Overweight/Obesity): A Scoping Review.

INTRODUCTION

Diabetes mellitus is the leading global cause of chronic kidney disease (CKD) and end-stage renal disease. Although cardiovascular outcomes have improved substantially, renal risk remains high. Glucagon-like peptide 1 (GLP-1) receptor agonists and the dual GLP-1/GIP agonist tirzepatide have demonstrated potential cardiorenal benefits, but renal evidence has not been systematically mapped across CKD stages and metabolic phenotypes. This scoping review aimed to identify and describe clinical evidence on renal outcomes associated with GLP-1-based therapies in adults with type 2 diabetes and/or overweight/obesity, with or without CKD.

METHODS

Following the Joanna Briggs Institute framework and PRISMA-ScR guidelines (protocol: OSF.IO/SZ87J), we searched PubMed, Embase, and CENTRAL from inception to October 2025. Eligible studies included phase 2-4 randomized controlled trials (RCTs), post hoc RCT analyses, and comparative observational studies reporting kidney outcomes. Data were charted using a structured extraction form with AI-assisted screening and manual validation. Risk of bias and certainty were appraised using RoB 2, ROBINS-I, and GRADE frameworks.

RESULTS

Of 607 records identified, 35 studies met inclusion criteria. Randomized evidence supports renal benefits for semaglutide, dulaglutide, and liraglutide, including reductions in composite kidney outcomes and slower eGFR decline. Tirzepatide demonstrated consistent albuminuria reductions and attenuation of eGFR decline compared with insulin glargine. Efpeglenatide, cotadutide, exenatide, and lixisenatide showed class-consistent antiproteinuric effects. Observational data extended findings to real-world and advanced CKD populations. Across agents, renal benefits were partly independent of glycemic and weight effects.

CONCLUSION

GLP-1-based therapies demonstrate consistent renoprotective signals across CKD stages and metabolic phenotypes, particularly in type 2 diabetes. Evidence is strongest for semaglutide and dulaglutide, with emerging data for tirzepatide and other incretin-based agents. These findings provide a structured evidence map to inform future consensus and clinical decision-making.