Microvascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review of Retinopathy and Nephropathy Evidence

TL;DR

This review finds that GLP-1 receptor agonists offer kidney benefits for type 2 diabetes patients but have inconclusive effects on retinopathy.

Contribution

The study systematically evaluates the microvascular effects of GLP-1 receptor agonists, highlighting their renal benefits and uncertain retinopathy impact.

Findings

GLP-1 receptor agonists show consistent renal protective effects, reducing nephropathy and macroalbuminuria.

Retinopathy outcomes remain inconclusive due to inconsistent results and limited event numbers.

Rapid glycemic improvement may transiently worsen retinopathy, but evidence is limited.

Abstract

This systematic review evaluated randomized controlled trials examining the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on microvascular outcomes in type 2 diabetes, focusing on diabetic retinopathy and nephropathy. Four eligible RCTs, enrolling over 27,000 patients with follow-up periods ranging from 32 weeks to 5.4 years, were included. GLP-1 receptor agonists consistently demonstrated renal protective effects, primarily driven by reductions in new or worsening nephropathy and macroalbuminuria, with more modest and inconsistent effects on estimated glomerular filtration rate (eGFR) decline. In contrast, their impact on retinopathy remained inconclusive. A transient signal of worsening retinopathy has been reported in the context of rapid glycemic improvement; however, across large outcome trials, effects on retinopathy have been inconsistent and remain inconclusive. Overall, the evidence for retinopathy risk is limited by small event numbers, heterogeneity in assessments, and exploratory analyses. The certainty of renal benefit was strengthened by rigorous trial designs and low risk of bias, whereas retinopathy outcomes were generally secondary and less robust. These findings suggest that GLP-1 receptor agonists can be prioritized for patients at high renal risk, but careful monitoring of individuals with pre-existing retinopathy remains warranted.

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