GLP-1s Move Beyond Diabetes as Core Kidney-Protective Therapy

Recent trial data have broadened the case for GLP-1 receptor agonists in kidney disease, pointing to a possible role beyond the drug class's original diabetes indication.

Translating that evidence into everyday practice hasn't necessarily kept pace, says Pranav Garimella, MD, chief medical officer at the American Kidney Fund, who points to cost, clinician unfamiliarity, and gaps in patient identification as ongoing barriers to access.

What Does the Evidence Show for GLP-1 Receptor Agonists in Kidney Disease?

• FLOW trial: In more than 3,500 participants with type 2 diabetes and CKD, semaglutide cut kidney-specific outcomes by 21% and slowed annual eGFR decline versus placebo.[1]
• SELECT trial: A 22% reduction in the composite kidney endpoint among non-diabetic participants with cardiovascular disease and obesity.[1]
• Non-diabetic CKD trial: Semaglutide cut a marker of kidney protein loss by roughly half over 24 weeks in people with overweight or obesity.[1]

"GLP-1 [receptor agonists] no longer belong just in the treatment of diabetes," Garimella has said, describing them as integral to preventing both heart failure and kidney disease progression. He frames them as complementary to RAS inhibitors, SGLT2 inhibitors, and nonsteroidal mineralocorticoid receptor antagonists (MRAs)—and, in select patients without significant proteinuria who have obesity, sleep apnea, or elevated heart failure risk, as a potential alternative to nonsteroidal MRAs. His approach broadly tracks the 2024 KDIGO CKD guideline, which pairs RAS/SGLT2 inhibitor therapy with emerging support for nonsteroidal MRAs and GLP-1 receptor agonists.

What Barriers Limit GLP-1 Receptor Agonist Use in Kidney Disease?

Garimella pointed to four first-line barriers still limiting access:

• Cost and coverage. "The ability to get these for all patients across all payers remains a challenge," he told HCPLive, noting that coverage criteria can differ by indication—diabetic kidney disease, heart failure, or obesity—so documenting the specific indication at prescribing matters.
• Clinician unfamiliarity. GLP-1s were historically viewed as diabetes-only drugs prescribed mainly by primary care and endocrinology. "Now we know that these medications can prevent kidney disease progression [and] heart disease progression, and so cardiologists and nephrologists are using them more often," Garimella said.
• Patient identification. Clinicians need to correctly flag patients with CKD alongside diabetes, obesity, or heart failure—including as a complementary option for patients who need to come off a drug class that's raising their potassium levels.
• Setting expectations. Not every patient tolerates the maximal dose. "We may need to back off to the best-tolerated dose, or even take patients off of it," Garimella said, adding that setting this expectation early keeps patients on therapy long enough to see benefit.

How Should Clinicians Discuss Weight Loss With GLP-1 Patients?

Garimella pushes back on the stigma that can surround weight-loss discussions in clinic. Central adiposity drives cardiac, kidney, and metabolic dysfunction, he said, so he frames GLP-1 therapy around long-term outcomes rather than the scale: "I show patients that this is doing more than just changing the numbers on the scale... The overarching goal is to connect that medication with the outcomes—not just the weight loss in the short term, but really those long-term outcomes that we're trying to prevent."

What's Next for GLP-1 Receptor Agonists in Kidney Disease?

GLP-1 receptor agonists are approaching standard therapy in the CKD toolkit, Garimella said, with wider use across disease states and combination therapies likely as data accumulates and FDA indications expand. Open questions remain: which patients benefit most versus those where risk outweighs benefit, how long therapy should continue, and how to manage patients who regain weight after stopping. Evidence is also thin in medically complex populations. "We don't know what the true benefits of GLP-1 receptor agonists are in patients who've received kidney transplants," he said, noting many still have diabetes, proteinuria, obesity, heart failure, or sleep apnea. "That is an area that is ripe for research still in the GLP-1 space."

Editor’s Note: Garimella reports no relevant disclosures.

References

1. Cooper ME, van Raalte DH. GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity. J Clin Invest. 2025;135(21):e194749. doi:10.1172/JCI194749

2. GLP-1 Receptor Agonists Reshape CKD Treatment Sequencing, With Pranav Garimella, MD. HCPLive. Published July 30, 2026. Accessed July 31, 2026. https://www.hcplive.com/view/glp-1-receptor-agonists-reshape-ckd-treatment-sequencing-with-pranav-garimella-md