Glucagon‐like peptide‐1 receptor agonists and kidney outcomes

Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Most supportive evidence of a kidney‐protective effect of the GLP‐1RA class of medications has been derived from kidney‐related outcomes reported from cardiovascular outcome trials (CVOTs). GLP‐1RAs have been shown to reduce albuminuria, mitigate cardiovascular risk, and possibly attenuate estimated glomerular filtration rate (eGFR) decline. The kidney‐protective effects of GLP‐1RAs are thought to be attributed to their anti‐inflammatory, antioxidant, and vasodilatory properties. Despite these promising findings, the use of GLP‐RAs has yet to be definitively shown to slow progression to chronic kidney failure in people with T2DM. The Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) is the first major trial assessing the potential of a GLP‐1RA to slow progression of kidney disease in people with established CKD to clinically important kidney end points. On March 5, 2024, the top line result from FLOW was announced with semaglutide 1.0 mg being reported to reduce the primary end point of the trial by a significant 24% compared with placebo. Here, we summarize the kidney outcomes reported from CVOTs for the GLP‐1RA class of medication and briefly describe kidney outcomes from other major GLP‐1RAs trials. We also discuss a potential role of the dual GLP‐1/glucose‐dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, as a kidney‐protective agent. Highlights Evidence from GLP‐1RAs CVOTs show that GLP‐1RAs reduce albuminuria but slowing of progression to chronic kidney failure remains to be proven. The FLOW trial is the first study assessing the usefulness of a once‐weekly subcutaneous GLP‐1RA (semaglutide) in slowing progression to clinically important kidney end points and protection form cardiovascular disease people with T2DM and established CKD. FLOW will help guide the optimal use of GLP‐1RAs in the clinical care of people with T2DM and CKD.