Potential kidney protective effects of glucagon‐like peptide‐1 receptor agonists

Jul 20, 2024Nephrology (Carlton, Vic.)

Possible kidney protection from drugs that activate glucagon-like peptide-1 receptors

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Abstract

The primary endpoint of the FLOW trial was reduced by 24% with both chronic kidney disease and cardiovascular outcomes contributing to risk reduction.

GLP-1 receptor agonists may reduce albuminuria and preserve kidney function in individuals with type 2 diabetes and chronic kidney disease.
These medications are associated with anti-inflammatory, antioxidant, and natriuretic properties that could provide kidney protection.
Despite promising results, definitive evidence that GLP-1 receptor agonists slow progression to chronic kidney failure or reduce related deaths is lacking.
The FLOW trial was halted due to efficacy concerns, indicating that further investigation is needed.

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes (T2DM) with chronic kidney disease (CKD). This class of medication has demonstrated promising results in reducing albuminuria, preserving estimated glomerular filtration rate (eGFR), and mitigating cardiovascular (CV) risk, making them potential therapeutic options for individuals with CKD. The kidney protective effects of GLP-1RAs extend beyond glycaemic control, and are thought to be attributed to their anti-inflammatory, antioxidant, and natriuretic properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure, or reduce CV and kidney related death in people with T2DM and CKD. The Research Study to See How Semaglutide (a once weekly subcutaneous administered GLP-1RA) Works Compared to Placebo in People with Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) was recently stopped because of efficacy. The primary end point for the FLOW trial consists of a composite endpoint of (i) onset of chronic kidney failure; (ii) death from kidney failure; (iii) cardiovascular death; and (iv) onset of a persistent ≥50% reduction in eGFR from baseline. It has also been reported by the sponsors of the trial that the primary end point of the trial was reduced by 24% with both CKD and CV outcomes contributing to risk reduction. In anticipation of the results of the FLOW trial being published, we review the current evidence surrounding kidney outcomes and proposed kidney protective pathways associated with GLP-1RA use.

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Potential kidney protective effects of glucagon‐like peptide‐1 receptor agonists

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