GLP-1 Receptor Agonists Cut Body Weight and Albuminuria in Diabetic and Nondiabetic Patients

Glucagon-like peptide-1 receptor agonists (GLP-1R agonists) are well-established for managing type 2 diabetes mellitus (T2DM), promoting weight loss, and reducing cardiovascular risk. While their kidney-protective effects are increasingly recognized in diabetic populations, it has been unclear whether these albuminuria-lowering benefits extend to individuals with chronic kidney disease (CKD) but without T2DM. Current standard-of-care often focuses on blood glucose and blood pressure control, but direct mechanisms for reducing albuminuria in non-diabetic CKD are a significant therapeutic gap that GLP-1R agonists might address.

Researchers conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided meta-analysis, including 10 randomized controlled trials (n=26,088). They compared glucagon-like peptide-1 receptor agonists against placebo or standard care. Primary outcomes assessed were change in body weight (kg) and percentage change in urinary albumin-to-creatinine ratio (UACR). Change in estimated glomerular filtration rate (eGFR) was a secondary outcome. Prespecified subgroup analyses, including glycemic status, and random-effects meta-regression were performed to explore heterogeneity. Risk of bias assessment (2.0) and sensitivity analyses were also applied.

Glucagon-like peptide-1 receptor agonists significantly reduced body weight, with a mean difference of -5.85 kg (95% confidence interval: -7.78 to -3.92). This effect was consistent across studies despite some heterogeneity. GLP-1R agonists also lowered urinary albumin-to-creatinine ratio (UACR) overall by a mean difference of -27.94% (95% confidence interval: -37.72 to -18.15). Stratified analyses revealed a precise reduction in patients with type 2 diabetes mellitus (T2DM) (mean difference, -25.70%; I2=0%). Importantly, a directionally concordant, though less precise, reduction was observed in populations without T2DM (mean difference, -30.93%; I2=96%).

A modest between-group difference in estimated glomerular filtration rate (eGFR) was also observed, with a mean difference of -0.82 mL/min/1.73 m2 (I2=0%). Meta-regression indicated that the UACR attenuation was greater with longer treatment duration and showed greater benefit with higher baseline albuminuria.