GLP-1 receptor agonists: kidney and cardiovascular outcomes in people with CKD
While randomised trials indicate that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer cardiovascular (CV) and kidney protection in people with type 2 diabetes, their effectiveness in individuals with reduced eGFR is unclear. Previous CV outcome trials mainly recruited participants with preserved eGFR.
The aim of the systematic review and meta-analysis by Chen and colleagues was to evaluate the kidney and CV protective effects of GLP-1 RAs in people with reduced baseline eGFR. A comprehensive search for published randomised controlled trials (RCTs) was conducted.
RCTs that enrolled adults (aged ≥18 years) with varying degrees of kidney function (including individuals with chronic kidney disease [CKD] characterised by a baseline eGFR of <60 mL/min/1.73 m2) were selected. The studies compared GLP-1 RAs with control treatments (placebo or other pre-assigned treatments) and assessed a composite kidney outcome, all-cause mortality or a composite CV outcome.
Of the 212 studies identified, 12 incorporating data and outcomes from 17,996 participants with a baseline eGFR <60 mL/min/1.73 m2 were included in the meta-analyses. All of the trials were judged to have an overall low risk of bias. Two independent investigators extracted the relevant data.
The risk of composite kidney outcome was significantly lower in the GLP-1 RA group (weighted event rate, 15.1%) compared to the placebo group (17.5%) (OR, 0.85 [95% CI, 0.77 to 0.94; P=0.001]), with low heterogeneity amongst the studies (I2<0.01%). Additionally, the GLP-1 RA group was associated with a reduced risk of a >30% eGFR decline (OR, 0.78 [0.66 to 0.92; P=0.004]), a >40% decline (OR, 0.76 [0.61 to 0.95; P=0.01]) and a >50% decline (OR, 0.72 [0.61 to 0.85; P<0.001]).
The all-cause mortality risk was lower in the GLP-1 RA group (weighted event rate, 10.6%) compared to the placebo group (13.2%) (OR, 0.77 [0.60 to 0.98; P=0.03]), with high heterogeneity (I2<71.6%).
The GLP-1 RA group also showed a significant reduction in composite CV outcome (weighted event rate 12.1%) compared to placebo (14.0%) (OR, 0.86 [0.74 to 0.99; P=0.03]), with moderate heterogeneity (I2<40.3%).
Further sensitivity analysis focused solely on the RTCs employing human GLP-1 backbone agents (dulaglutide, liraglutide, semaglutide and albiglutide). It suggested that use of these GLP-1 RAs further lowered the risk of composite kidney outcome (OR, 0.83 [0.75 to 0.92; P=0.001]), all-cause mortality (OR, 0.70 [0.55 to 0.89; P=0.003]) and composite CV outcome (OR, 0.78 [0.70 to 0.87; P=0.001]) compared to placebo.
The investigators acknowledged some limitations, including the inconsistent kidney outcome definitions used in the studies and their focus on populations with type 2 diabetes, and potential publication bias. However, they concluded that the use of GLP-1 RAs offers multiple kidney and CV benefits to people with CKD.
The full article can be read here.
