Treating Obesity to Protect the Kidneys: How GLP-1 Drugs and Combined Therapies Are Changing CKD Management | Research

The takeaway

A multitargeted approach combining GLP-1 receptor agonists, SGLT2 inhibitors, and finerenone with standard RAAS blockade shows promise for protecting both heart and kidneys in patients with obesity and chronic kidney disease.

Multitargeted cardio-renal protection
Combining GLP-1 RAs, SGLT2 inhibitors, and finerenone with RAAS blockade creates a layered defense for both kidneys and heart in patients with obesity and CKD

What the researchers found

The review identifies a paradigm shift in CKD management: obesity-associated CKD phenotypes can now be therapeutically targeted using combinations of GLP-1 receptor agonists, SGLT2 inhibitors, and finerenone added to standard RAAS blockade. These multitargeted strategies address the pathophysiological interplay between obesity, metabolic syndrome, and kidney disease, with evidence of cardio-renal protection that could substantially alter disease progression.

Why it matters

CKD affects hundreds of millions of people worldwide, and obesity is both a major cause and accelerator of kidney disease. Until recently, treatment options were limited to RAAS blockade alone. The emergence of GLP-1 receptor agonists and other peptide-based therapies as cardio-renal protective agents represents a fundamental shift — obesity in CKD is now a treatable risk factor rather than an accepted comorbidity, potentially changing outcomes for millions of patients.

How the study worked

This is a narrative review synthesizing current evidence on the pathophysiology of obesity-related CKD, distinct clinical phenotypes associated with CKD progression, and the emerging therapeutic landscape including GLP-1 receptor agonists, SGLT2 inhibitors, and finerenone. No new experimental data were generated.

What this study cannot tell us

As a narrative review, this paper reflects the authors' interpretation of existing evidence rather than a systematic analysis. The cardio-renal benefits of GLP-1 receptor agonists in CKD patients specifically with obesity are extrapolated partly from trials in broader populations. Long-term outcomes of these multitargeted combinations remain to be established in dedicated CKD+obesity trials.

How to read the evidence

This is a narrative review synthesizing evidence from clinical trials and mechanistic studies. While it provides a comprehensive overview and clinical framework, it does not follow systematic review methodology and reflects the authors' expert interpretation.

When this study was published

Published in 2025, this review captures the current state of a rapidly evolving field, including the latest evidence on GLP-1 receptor agonists and combination therapies for CKD.

The bigger picture

This review reflects a broader trend in medicine: GLP-1 receptor agonists, originally developed for diabetes, are being recognized as cardio-renal protective agents across a widening range of conditions. The concept of treating obesity not just for weight loss but to directly protect organs like the kidneys is reshaping nephrology practice and expanding the clinical utility of peptide-based therapies far beyond their original indications.

Questions still open

What are the optimal combinations and sequencing of GLP-1 receptor agonists, SGLT2 inhibitors, and finerenone for different CKD stages and obesity phenotypes?
Can aggressive early treatment of obesity with peptide-based therapies prevent CKD progression in at-risk patients before significant kidney damage occurs?
How do newer multi-receptor agonists like tirzepatide and retatrutide compare to single GLP-1 receptor agonists for renal protection in obese CKD patients?

Common questions

Can GLP-1 drugs protect the kidneys in people with obesity?

Emerging evidence suggests yes. GLP-1 receptor agonists, originally developed for diabetes and weight loss, are showing cardio-renal protective effects in patients with obesity and chronic kidney disease. When combined with SGLT2 inhibitors and other medications, they may significantly slow kidney disease progression — a major shift in how nephrologists approach obesity-related CKD.

Why does obesity make kidney disease worse?

Obesity creates a harmful metabolic environment for the kidneys through multiple pathways: increased inflammation, insulin resistance, high blood pressure, and direct fat accumulation in and around the kidneys. These factors accelerate kidney damage and CKD progression. Treating obesity can interrupt these pathways and slow kidney decline, which is why new weight-loss medications like GLP-1 receptor agonists are becoming part of CKD treatment strategies.

Read the original research

Obesity as a modifiable risk factor in patients with chronic kidney disease.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

View on PubMed ↗Publisher’s paper ↗

Citation

Morales, Enrique; Jenssen, Trond G; Bevc, Sebastjan; Miglinas, Marius; Martin, William P; Theodorakopoulou, Marieta; Buus Jørgensen, Morten; Trillini, Matias. (2025). Obesity as a modifiable risk factor in patients with chronic kidney disease.. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. https://doi.org/10.1093/ndt/gfaf231