The Impact of Glucagon-like Peptide-1 Receptor Agonists on Kidney Outcomes: A Meta-Analysis of Randomized Placebo-Controlled Trials

Key Points This is an updated meta-analysis about glucagon-like peptide-1 receptor agonists (GLP-1 RAs) incorporating findings from the recently published FLOW and SELECT studies. Our findings show that GLP-1 RAs reduce kidney disease progression in patients with type 2 diabetes or overweight/obesity status, with or without CKD. Our meta-analysis supports the use of GLP-1 RAs for reducing the risk of adverse kidney outcomes across different populations. Background Recent data indicate a potential benefit of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on the progression of kidney disease among patients with CKD. Our aim was to evaluate the effect of GLP-1 RAs on the risk of worsening kidney function across different populations. Methods We conducted a meta-analysis of randomized controlled trials that tested GLP-1 RA treatment versus placebo in individuals with type 2 diabetes or with overweight/obesity status, with or without CKD, with kidney events reported as primary or secondary end points. The primary outcome was the occurrence of worsening kidney function, defined as either a doubling of serum creatinine or a ≥40% or ≥50% decline in eGFR, according to each study report. Secondary outcomes included development of persistent macroalbuminuria and a composite of worsening kidney function or the development of persistent macroalbuminuria. Subgroup analyses were performed by eGFR and albuminuria categories. The results are presented as risk ratios with 95% confidence intervals. Results Eight trials were eligible, including a total of 68,572 patients, of whom 34,042 (49.6%) received GLP-1 RA treatment. During follow-up, 1028 participants receiving GLP-1 RA (3.0%) and 1150 participants receiving placebo (3.5%) experienced worsening kidney function. Treatment with GLP-1 RAs (versus placebo) resulted in a reduction in the risk of worsening kidney function (risk ratios, 0.84; 95% confidence interval, 0.77 to 0.91; P < 0.001). In addition, treatment with GLP-1 RAs significantly reduced the risk of developing persistent macroalbuminuria and the risk of the composite outcome of worsening kidney function or development of persistent macroalbuminuria. The results were consistent in patients with and without CKD. Conclusions In conclusion, our meta-analysis suggests that GLP-1 RA reduce kidney disease progression in type 2 diabetes or overweight/obesity regardless of CKD status.