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

datacite.rightshttp://purl.org/coar/access_right/c_abf2
dc.contributor.authorRico‑Fontalvo, Jorge
dc.contributor.authorDaza‑Arnedo, Rodrigo
dc.contributor.authorElbert, Alicia
dc.contributor.authorCorrea‑Rotter, Ricardo
dc.contributor.authorDina‑Batlle, Eliana
dc.contributor.authorLorca‑Herrera, Eduardo
dc.contributor.authorProença de Moraes, Thyago
dc.contributor.authorSánchez‑Polo, Vicente
dc.contributor.authorBuiles‑Montaño, Carlos E.
dc.date.accessioned2026-03-20T20:32:29Z
dc.date.available2026-03-20T20:32:29Z
dc.date.issued2026
dc.description.abstractIntroduction: 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.eng
dc.format.mimetypepdf
dc.identifier.citationRico-Fontalvo, J., Daza-Arnedo, R., Elbert, A. et al. 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. Diabetes Ther (2026).
dc.identifier.doihttps://doi.org/10.1007/s13300-026-01854-8
dc.identifier.issn1869-6961(electrónico)
dc.identifier.issn1869-6953 (Impreso)
dc.identifier.urihttps://hdl.handle.net/20.500.12442/17449
dc.identifier.urlhttps://link.springer.com/article/10.1007/s13300-026-01854-8#citeas
dc.language.isoeng
dc.publisherSpringer Naturespa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.sourceDiabetes Therapyeng
dc.sourceDiabetes Thereng
dc.sourceVol. 17 No. 3 Año 2026spa
dc.subject.keywordsChronic kidney diseaseeng
dc.subject.keywordsRenal outcomeseng
dc.subject.keywordsAlbuminuriaeng
dc.subject.keywordseGFR slopeeng
dc.subject.keywordsGLP-1 receptor agonisteng
dc.subject.keywordsTirzepatideeng
dc.subject.keywordsType 2 diabeteseng
dc.subject.keywordsObesityeng
dc.subject.keywordsScoping revieweng
dc.subject.keywordsEvidence mapeng
dc.titleRenal Outcomes of GLP‑1 Receptor Agonists and Tirzepatide Across CKD Stages and Metabolic Phenotypes (Type 2 Diabetes and/or Overweight/ Obesity): A Scoping Revieweng
dc.type.driverinfo:eu-repo/semantics/article
dc.type.spaArtículo científico
dcterms.referencesIDF Diabetes Atlas. 11 ed. Brussels, Belgium: International Diabetes Federation; 2025.eng
dcterms.referencesMuskiet MHA, Tonneijck L, Smits MM, et al. GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nat Rev Nephrol. 2017;13(10):605–28. https:// doi. org/ 10. 1038/ nrneph. 2017. 123.eng
dcterms.referencesSourris KC, Ding Y, Maxwell SS, et al. Glucagonlike peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products-induced inflammation. Kidney Int. 2024;105(1):132–49. https:// doi. org/ 10. 1016/j. kint. 2023. 09. 029.eng
dcterms.referencesMarso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834– 44. https:// doi. org/ 10. 1056/ NEJMo a1607 141.eng
dcterms.referencesTuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, openlabel, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605–17. https:// doi. org/ 10. 1016/ s2213-​8587(18) 30104-9.eng
dcterms.referencesFitch K, Bernstein SJ, Aguilar MD, et al. RAND/ UCLA appropriateness method user’s manual: RAND corporation Santa Monica, CA; 2000.eng
dcterms.referencesPollock D, Peters MDJ, Khalil H, et al. Recommendations for the extraction, analysis, and presentation of results in scoping reviews. JBI Evid Synth. 2023;21(3):520–32. https:// doi. org/ 10. 11124/ jbies-​22-​00123.eng
dcterms.referencesTricco AC, Lillie E, Zarin W, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467–73. https:// doi. org/ 10. 7326/ m18-​0850.eng
dcterms.referencesOuzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. https:// doi. org/ 10. 1186/ s13643-​016-​0384-4.eng
dcterms.referencesSterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. https:// doi. org/ 10. 1136/ bmj. l4898.eng
dcterms.referencesSterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. https:// doi. org/ 10. 1136/ bmj. i4919.eng
dcterms.referencesGuyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6. https:// doi. org/ 10. 1136/ bmj. 39489. 470347. AD.eng
dcterms.referencesPerkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109–21. https:// doi. org/ 10. 1056/ NEJMo a2403 347.eng
dcterms.referencesMcGuire DK, Marx N, Mulvagh SL, et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med. 2025;392(20):2001– 12. https:// doi. org/ 10. 1056/ NEJMo a2501 006.eng
dcterms.referencesVernstrøm L, Gullaksen S, Sørensen SS, et al. Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial. Diabetologia. 2024;67(10):2175–87. https:// doi. org/ 10. 1007/ s00125-​024-​06228-y.eng
dcterms.referencesde García Lucas MD, Caballero I, Fernández-García JC, et al. Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. Front Endocrinol. 2023;14:1240279. https:// doi. org/ 10. 3389/ fendo. 2023. 12402 79.eng
dcterms.referencesLong JJ, Sahi SS, Lemke AI, et al. The use of semaglutide in patients with renal failure-a retrospective cohort study. Endocr Pract. 2024;30(10):963– 9. https:// doi. org/ 10. 1016/j. eprac. 2024. 07. 008.eng
dcterms.referencesColhoun HM, Lingvay I, Brown PM, et al. Longterm kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024;30(7):2058–66. https:// doi. org/ 10. 1038/ s41591-​024-​03015-5.eng
dcterms.referencesApperloo EM, Gorriz JL, Soler MJ, et al. Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial. Nat Med. 2025;31(1):278–85. https:// doi. org/ 10. 1038/ s41591-​024-​03327-6.eng
dcterms.referencesHeerspink HL, Tuttle KR, Pavo I, et al. Tirzepatide reduces albuminuria in patients with T2D: post-hoc pooled analysis of SURPASS 1-5. Diabetol Stoffwechs. 2024;19:S75. https:// doi. org/ 10. 1055/s-​0044-​17853 84.eng
dcterms.referencesHeerspink HJL, Sattar N, Pavo I, et al. Effects of tirzepatide versus insulin glargine on cystatin C-based kidney function: a SURPASS-4 post hoc analysis. Diabetes Care. 2023;46(8):1501–6. https:// doi. org/ 10. 2337/ dc23-​0261eng
dcterms.referencesApperloo EM, Tuttle KR, Pavo I, et al. Tirzepatide associated with reduced albuminuria in participants with type 2 diabetes: pooled post hoc analysis from the randomized active- and placebocontrolled SURPASS-1-5 clinical trials. Diabetes Care. 2025;48(3):430–6. https:// doi. org/ 10. 2337/ dc24-​1773.eng
dcterms.referencesPacker M, Zile MR, Kramer CM, Murakami M, Ou Y, Borlaug BA. Interplay of chronic kidney disease and the effects of tirzepatide in patients with heart failure, preserved ejection fraction, and obesity: the SUMMIT trial. J Am Coll Cardiol. 2025;85(18):1721–35. https:// doi. org/ 10. 1016/j. jacc. 2025. 03. 009.eng
dcterms.referencesOe Y, Nomoto H, Cho KY, et al. Efficacy and safety of tirzepatide in subjects with type 2 diabetes and chronic kidney disease: a prospective, two-arm observational study. Ther Adv Endocrinol Metab. 2025. https:// doi. org/ 10. 1177/ 20420 18825 13782 16.eng
dcterms.referencesKarakasis P, Patoulias D, Fragakis N, Klisic A, Rizzo M. Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: a systematic review and multilevel metaanalysis. Diabetes Obes Metab. 2024;26(3):1090– 104. https:// doi. org/ 10. 1111/ dom. 15410.eng
dcterms.referencesGerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019;394(10193):131–8. https:// doi. org/ 10. 1016/ S0140-​6736(19) 31150-X.eng
dcterms.referencesTuttle KR, Rayner B, Lakshmanan MC, et al. Clinical outcomes by albuminuria status with dulaglutide versus insulin glargine in participants with diabetes and CKD: AWARD-7 exploratory analysis. Kidney360. 2021;2(2):254–62. https:// doi. org/ 10. 34067/ KID. 00058 52020.eng
dcterms.referencesTuttle KR, McKinney TD, Davidson JA, Anglin G, Harper KD, Botros FT. Effects of once-weekly dulaglutide on kidney function in patients with type 2 diabetes in phase II and III clinical trials. Diabetes Obes Metab. 2017;19(3):436–41.eng
dcterms.referencesTsuchida KI, Taneda S, Yokota I, et al. The renoprotective effect of once-weekly GLP-1 receptor agonist dulaglutide on progression of nephropathy in Japanese patients with type 2 diabetes and moderate to severe chronic kidney disease (JDDM67). J Diabetes Investig. 2022;13(11):1834–41. https:// doi. org/ 10. 1111/ jdi. 13877.eng
dcterms.referencesMarso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. https:// doi. org/ 10. 1056/ NEJMo a1603 827.eng
dcterms.referencesDavies MJ, Bain SC, Atkin SL, et al. Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRARENAL): a randomized clinical trial. Diabetes Care. 2016;39(2):222–30. https:// doi. org/ 10. 2337/ dc14-​2883.eng
dcterms.referencesvon Scholten BJ, Lajer M, Goetze JP, Persson F, Rossing P. Time course and mechanisms of the anti-hypertensive and renal effects of liraglutide treatment. Diabet Med. 2015;32(3):343–52. https:// doi. org/ 10. 1111/ dme. 12594.eng
dcterms.referencesvon Scholten BJ, Persson F, Rosenlund S, et al. The effect of liraglutide on renal function: a randomized clinical trial. Diabetes Obes Metab. 2017;19(2):239–47. https:// doi. org/ 10. 1111/ dom. 12808.eng
dcterms.referencesImamura S, Hirai K, Hirai A. The glucagon-like peptide-1 receptor agonist, liraglutide, attenuates the progression of overt diabetic nephropathy in type 2 diabetic patients. Tohoku J Exp Med. 2013;231(1):57–61. https:// doi. org/ 10. 1620/ tjem. 231. 57.eng
dcterms.referencesGerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385(10):896–907.eng
dcterms.referencesSelvarajah V, Robertson D, Hansen L, et al. A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease. Kidney Int. 2024;106(6):1170–80. https:// doi. org/ 10. 1016/j. kint. 2024. 08. 023.eng
dcterms.referencesParker VER, Hoang T, Schlichthaar H, et al. Efficacy and safety of cotadutide, a dual glucagonlike peptide-1 and glucagon receptor agonist, in a randomized phase 2a study of patients with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab. 2022;24(7):1360–9. https:// doi. org/ 10. 1111/ dom. 14712.eng
dcterms.referencesWang X, Zhang H, Zhang Q, et al. Exenatide and renal outcomes in patients with type 2 diabetes and diabetic kidney disease. Am J Nephrol. 2020;51(10):806–14. https:// doi. org/ 10. 1159/ 00051 0255.eng
dcterms.referencesvan der Aart-van der Beek AB, Clegg LE, Penland RC, et al. Effect of once-weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: a post hoc analysis of the EXSCEL trial. Diabetes Obes Metab. 2020;22(12):2493– 8. https:// doi. org/ 10. 1111/ dom. 14175.eng
dcterms.referencesvan der Aart-van der Beek AB, van Raalte DH, Guja C, et al. Exenatide once weekly decreases urinary albumin excretion in patients with type 2 diabetes and elevated albuminuria: pooled analysis of randomized active controlled clinical trials. Diabetes Obes Metab. 2020;22(9):1556–66. https:// doi. org/ 10. 1111/ dom. 14067.eng
dcterms.referencesMuskiet MHA, Tonneijck L, Huang Y, et al. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2018;6(11):859–69. https:// doi. org/ 10. 1016/ S2213-​8587(18) 30268-7.eng
dcterms.referencesMuta Y, Kobayashi K, Toyoda M, et al. Influence of combination therapy with dulaglutide or liraglutide and SGLT2 inhibitors on renal outcomes in patients with type 2 diabetes: a post-hoc analysis of the RECAP study. Tokai J Experiment Clin Med. 2025;50(1):1–9.eng
dcterms.referencesDai JW, Lin Y, Li XW, et al. Comparative cardiovascular and renal outcomes of Liraglutide versus dulaglutide in Asian type 2 diabetes patients. Sci Rep. 2024;14(1):27491.eng
dcterms.referencesClegg LE, Penland RC, Bachina S, et al. Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes: insights from the EXSCEL trial. Cardiovasc Diabetol. 2019;18(1):138. https:// doi. org/ 10. 1186/ s12933-​019-​0942-x.eng
dcterms.referencesCai YX, Liu FH, Sun JH, Lin CH. The cardiovascular outcomes between liraglutide and dulaglutide among different chronic kidney disease stages in patients with type 2 diabetes. Endocr Pract. 2025;31(3):292–7. https:// doi. org/ 10. 1016/j. eprac. 2024. 11. 016.eng
dcterms.referencesTuttle KR, Bjornstad P, Pruijm M, et al. Mechanistic effects of semaglutide on kidney disease in type 2 diabetes: the REMODEL trial. [Poster]. In press 2025.eng
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