GLP-1 drugs on dialysis: an editorial weighs encouraging signals against the trials still needed

The background

GLP-1 receptor agonists slowed kidney disease and reduced cardiovascular events in people with type 2 diabetes and proteinuric CKD with an eGFR above 25, in the FLOW trial of semaglutide. They are not currently recommended below an eGFR of 25 or for people on kidney replacement therapy. Dr. Csaba Kovesdy of the University of Tennessee Health Science Center points out that this is because large randomized trials have not been done in that population, not because of a pharmacokinetic problem. The exception is exenatide, which is cleared by the kidney and should not be used.

The study he discusses

The editorial accompanies a real-world study by Karpinski and colleagues in the same journal. NephSpace has not yet read that study, so the figures here are as the editorial reports them. The study included 2,492 patients who were taking a GLP-1 receptor agonist when they started kidney replacement therapy between 2014 and 2018, matched with similar patients who were not. GLP-1 receptor agonist use was associated with a 17% lower risk of death and a 9% lower risk of hospitalization, consistent across sensitivity analyses and for dulaglutide, liraglutide and semaglutide separately.

His reading of the evidence

• Strengths: a relatively large, contemporary treated group, careful matching, clinically relevant end points including hospitalization, and analyses by individual drug.
• Prevalent users: patients were already on the drug when they entered the study. That favors people who tolerated it and stayed on it, and misses early effects.
• No active comparator: the comparison group was untreated, rather than taking another drug for the same purpose, which leaves room for confounding by indication, healthy-user effects and differences in access to care.
• Other limits: all-cause rather than cardiovascular death, no transplant-waitlisting outcome, and no information on why the drug was prescribed.
• Still, he finds it reassuring that the results agree with trials in other populations and with earlier real-world studies in kidney failure, which followed new users of the drug, one of them against an active comparator.

Why caution on dialysis

Dr. Kovesdy raises concerns specific to dialysis. Protein-energy wasting may affect up to about 43% of patients on kidney replacement therapy, and appetite suppression could make it worse. With weight-loss treatments in general, up to about a quarter of the weight lost can be muscle, and weight regained after stopping is mostly fat, which risks sarcopenic obesity. Hypoglycemia is common in kidney failure, and the risk rises when a GLP-1 receptor agonist is combined with insulin or other glucose-lowering drugs. He calls for large randomized trials of efficacy and safety or, failing that, better data on how different agents and doses affect tolerance and body composition.

Caveats

This is an expert editorial, not new data, and the study it discusses is observational, so it shows associations rather than proof of benefit.

Disclosures: Dr. Kovesdy reports consulting, honoraria and research funding from several companies, listed with the editorial, including AstraZeneca, Bayer and Boehringer Ingelheim. He leads the nephrology division at UTHSC and is Dr. Wael Hussein's department chief.

The source: Kovesdy CP. Glucagon-Like Peptide-1 Receptor Agonists in Dialysis: The Evidence Grows, but Trials Must Follow. Clin J Am Soc Nephrol. Published online ahead of print October 1, 2026 (editorial). doi:10.2215/CJN.0000001256 Read the original

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