Kidney and Cardiovascular Outcomes Among Patients With CKD Receiving GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomized Trials

Abstract

Rationale & objective: Glucagon-like peptide 1 (GLP-1) receptor agonists improve cardiac and kidney outcomes in patients with diabetes; however, their efficacy in individuals with reduced estimated glomerular filtration rate (eGFR) is uncertain. This study evaluated the effects of GLP-1 receptor agonists on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD).

Study design: Systematic review and meta-analysis of randomized controlled trials (RCTs) reported through May 25, 2024.

Setting & study populations: Adult participants in RCTs with baseline eGFR<60mL/min/1.73m².

Selection criteria for studies: RCTs including adults (≥18 years old) with varying degrees of kidney function, including individuals with CKD characterized by a baseline eGFR of<60mL/min/1.73m², that compared GLP-1 receptor agonists with control treatments with respect to a composite kidney outcome, all-cause mortality, or a composite CV disease outcome. From among 212 screened studies, 12 trials involving that included participants with baseline eGFR<60mL/min/1.73m² were included.

Data extraction: Two independent investigators extracted the data.

Analytical approach: Pooled odds ratios (ORs) for composite kidney outcome, all-cause mortality, and composite CV outcome were estimated using random-effects models. Evidence certainty was assessed using the GRADE system.

Results: The analyses included 17,996 RCT participants with baseline eGFR<60mL/min/1.73m². GLP-1 receptor agonists were significantly associated with a reduced risk of the composite kidney outcome (OR, 0.85 [95% CI, 0.77-0.94]; P=0.001) with low heterogeneity (I²<0.01%). GLP-1 receptor agonists were also associated with a reduced the risk of a>30% eGFR decline (OR, 0.78; P=0.004), a>40% decline (OR, 0.76; P=0.01), and a>50% decline (OR, 0.72; P<0.001). Risk of all-cause mortality was also lower in the GLP-1 receptor agonist group (OR, 0.77 [95% CI, 0.60-0.98], P=0.03), though there was high heterogeneity (I²=71.6%). Composite CV outcomes were also lower with the use of a GLP-1 receptor agonist (OR, 0.86 [95% CI, 0.74-0.99], P=0.03; I²=40.3%). Sensitivity analyses restricted to human GLP-1 backbone agents showed enhanced benefits.

Limitations: Inconsistent kidney outcome definitions, focus on diabetic populations in most studies, and potential publication bias.

Conclusions: GLP-1 receptor agonists improved kidney and CV outcomes, and survival in patients with CKD enrolled in an array of clinical trials.

Registration: Registered at PROSPERO with identification number CRD42023449059.

Plain-language summary: Glucagon-like peptide 1 (GLP-1) receptor agonists reduce body weight and improve glycemic control. They also have been shown to protect the heart and kidney in people with diabetes. However, the extrapolation of these findings to those with chronic kidney disease (CKD) is uncertain. This study meta-analyzed data from clinical trials focusing on patients with CKD and noted that GLP-1 receptor agonists may slow kidney disease progression and lower the risk of heart disease, stroke, and death. These findings suggest that GLP-1 receptor agonists offer multiple kidney and cardiovascular benefits to people with CKD.

Keywords: Cardiovascular outcome; chronic kidney disease; diabetes mellitus; incretins; kidney failure; major adverse cardiac event; mortality.