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Purpose <p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus, offering glycemic, cardiovascular, and renal benefits; however, their impact on diabetic retinopathy (DR) remains uncertain.</p> Methods <p>We conducted a PRISMA 2020-guided systematic review prospectively registered in PROSPERO (CRD420251237987). We searched bibliographic databases and ClinicalTrials.gov through 31 October 2025 for studies reporting DR outcomes in adults with type 2 diabetes treated with GLP-1 RAs.</p> Results <p>Thirty-one studies were included: ten randomized evidence reports (five major randomized controlled trials (RCTs) and five RCT-derived secondary or post hoc analyses) and twenty-one observational/real-world studies. Heterogeneity in baseline DR status, outcome definitions, outcome ascertainment methods, and follow-up precluded quantitative pooling. Aside from SUSTAIN-6—where DR complications showed a signal consistent with early worsening in the setting of rapid HbA1c reduction—no randomized trial demonstrated increased DR progression. Major cardiovascular outcome trials (LEADER, REWIND, EXSCEL, HARMONY) reported neutral retinal outcomes but largely relied on adverse-event reporting rather than standardized ophthalmic grading. Real-world cohorts yielded heterogeneous estimates, and residual confounding cannot be excluded, particularly where baseline retinopathy severity was incompletely characterized.</p> Conclusion <p>Current evidence regarding the effects of GLP-1 RAs on DR outcomes remains inconsistent, with no convincing evidence supporting an intrinsic retinotoxic effect. These findings reinforce the importance of baseline ophthalmic assessment and closer monitoring when advanced pre-existing DR and rapid glycemic improvement is anticipated. Interpretation of the various studies remains limited by heterogeneity in methods, outcome definitions, follow-up duration, and the lack of standardized retinal assessment protocols, including best-corrected visual acuity, fundus photography and limited use of OCT to adequately evaluate both macular and peripheral retinal disease.</p>

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Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: a systematic review of diabetic retinopathy outcomes

  • 期刊论文

  • 发表日期：

    2026年8月1日

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  • Catarina Francisco,
  • João Sérgio Neves,
  • Rita Laiginhas,
  • Manuel Falcão

摘要

Purpose

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus, offering glycemic, cardiovascular, and renal benefits; however, their impact on diabetic retinopathy (DR) remains uncertain.

Methods

We conducted a PRISMA 2020-guided systematic review prospectively registered in PROSPERO (CRD420251237987). We searched bibliographic databases and ClinicalTrials.gov through 31 October 2025 for studies reporting DR outcomes in adults with type 2 diabetes treated with GLP-1 RAs.

Results

Thirty-one studies were included: ten randomized evidence reports (five major randomized controlled trials (RCTs) and five RCT-derived secondary or post hoc analyses) and twenty-one observational/real-world studies. Heterogeneity in baseline DR status, outcome definitions, outcome ascertainment methods, and follow-up precluded quantitative pooling. Aside from SUSTAIN-6—where DR complications showed a signal consistent with early worsening in the setting of rapid HbA1c reduction—no randomized trial demonstrated increased DR progression. Major cardiovascular outcome trials (LEADER, REWIND, EXSCEL, HARMONY) reported neutral retinal outcomes but largely relied on adverse-event reporting rather than standardized ophthalmic grading. Real-world cohorts yielded heterogeneous estimates, and residual confounding cannot be excluded, particularly where baseline retinopathy severity was incompletely characterized.

Conclusion

Current evidence regarding the effects of GLP-1 RAs on DR outcomes remains inconsistent, with no convincing evidence supporting an intrinsic retinotoxic effect. These findings reinforce the importance of baseline ophthalmic assessment and closer monitoring when advanced pre-existing DR and rapid glycemic improvement is anticipated. Interpretation of the various studies remains limited by heterogeneity in methods, outcome definitions, follow-up duration, and the lack of standardized retinal assessment protocols, including best-corrected visual acuity, fundus photography and limited use of OCT to adequately evaluate both macular and peripheral retinal disease.