Across 10 randomized controlled trials enrolling 26,088 participants, GLP-1 receptor agonists produced a mean body weight reduction of 5.85 kg and a 27.94% decrease in urinary albumin-to-creatinine ratio (UACR) versus placebo or standard care. The albuminuria reduction was precise in type 2 diabetes populations (−25.70%, I²=0%) and directionally consistent but more heterogeneous in non-diabetic cohorts (−30.93%, I²=96%). A modest eGFR difference of −0.82 mL/min/1.73m² was observed. Meta-regression identified higher baseline albuminuria as predicting greater UACR benefit, while longer treatment duration attenuated the effect.
The kidney-protective signal extending beyond glycemic populations is the most consequential element here. Until recently, GLP-1 agents were framed primarily as metabolic drugs; the FLOW trial's 2024 demonstration of hard renal endpoints with semaglutide in CKD patients has rapidly reframed this class as nephroprotective independent of diabetes status. This meta-analysis adds quantitative weight to that pivot, though the I²=96% heterogeneity in non-diabetic subgroups demands caution — pooling diverse CKD etiologies likely obscures meaningful variation in response. The modest eGFR signal is not alarming and mirrors known hemodynamic effects of RAAS inhibitors at initiation. Practically, adults with proteinuric kidney disease — diabetic or otherwise — may benefit from GLP-1 therapy beyond weight loss alone. Evidence certainty is moderate for UACR, appropriately reflecting residual heterogeneity. Confirmatory dedicated trials in non-diabetic CKD remain the needed next step.