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Background <p>Diabetic retinopathy (DR) is a significant cause of vision impairment in patients with diabetes. The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the progression of DR remains unclear. This systematic review and meta-analysis aimed to evaluate the association between GLP-1RA therapy and DR progression.</p> Methods <p>A comprehensive search of electronic databases identified 161 records, of which 11 studies met the inclusion criteria. Included studies comprised randomized controlled trials (RCTs) and retrospective cohort studies conducted in North America, Europe, and East Asia, with sample sizes ranging from 137 to 9,463 participants. The primary GLP-1RAs analyzed were albiglutide, liraglutide, semaglutide, exenatide, and dulaglutide, compared to either placebo or SGLT-2 inhibitors. The primary outcome was DR progression, assessed through pooled relative risk (RR) estimates using a random-effects model. Subgroup analyses were conducted by GLP-1RA type and geographical location. Sensitivity analyses and assessment of publication bias (via funnel plot, Egger’s test, and Begg’s test) were performed. Risk of bias was evaluated using the Cochrane tool.</p> Results <p>The meta-analysis indicated no statistically significant association between GLP-1RA use and DR progression (pooled RR = 1.07, 95% confidence interval [CI]: 0.90–1.28). Subgroup analyses by GLP-1RA type and geographical location also showed no significant differences. However, semaglutide demonstrated the highest RR for DR progression in two studies (RR = 1.76 [1.11–2.79] and RR = 6.41 [0.67–61.46]), a unique finding contrasting with the overall results. Sensitivity analyses confirmed the robustness of the findings, and no publication bias was detected (<i>P</i> &gt; 0.05 for Egger’s and Begg’s tests). Risk of bias analysis revealed a low risk across most domains.</p> Conclusion <p>This meta-analysis suggests that GLP-1RA therapy is not significantly associated with an increased risk of DR progression. However, heterogeneity in outcomes, particularly with semaglutide, warrants further investigation.</p> Trial registration <p>PROSPERO CRD420251007882.</p> Clinical trial number <p>Not applicable.</p>

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Assessing the risk of diabetic retinopathy progression with GLP-1 receptor agonists: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月30日

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  • Qian Yang,
  • Waseem Hassan,
  • Hammad Ahmed,
  • Haiyan Zheng

摘要

Background

Diabetic retinopathy (DR) is a significant cause of vision impairment in patients with diabetes. The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the progression of DR remains unclear. This systematic review and meta-analysis aimed to evaluate the association between GLP-1RA therapy and DR progression.

Methods

A comprehensive search of electronic databases identified 161 records, of which 11 studies met the inclusion criteria. Included studies comprised randomized controlled trials (RCTs) and retrospective cohort studies conducted in North America, Europe, and East Asia, with sample sizes ranging from 137 to 9,463 participants. The primary GLP-1RAs analyzed were albiglutide, liraglutide, semaglutide, exenatide, and dulaglutide, compared to either placebo or SGLT-2 inhibitors. The primary outcome was DR progression, assessed through pooled relative risk (RR) estimates using a random-effects model. Subgroup analyses were conducted by GLP-1RA type and geographical location. Sensitivity analyses and assessment of publication bias (via funnel plot, Egger’s test, and Begg’s test) were performed. Risk of bias was evaluated using the Cochrane tool.

Results

The meta-analysis indicated no statistically significant association between GLP-1RA use and DR progression (pooled RR = 1.07, 95% confidence interval [CI]: 0.90–1.28). Subgroup analyses by GLP-1RA type and geographical location also showed no significant differences. However, semaglutide demonstrated the highest RR for DR progression in two studies (RR = 1.76 [1.11–2.79] and RR = 6.41 [0.67–61.46]), a unique finding contrasting with the overall results. Sensitivity analyses confirmed the robustness of the findings, and no publication bias was detected (P > 0.05 for Egger’s and Begg’s tests). Risk of bias analysis revealed a low risk across most domains.

Conclusion

This meta-analysis suggests that GLP-1RA therapy is not significantly associated with an increased risk of DR progression. However, heterogeneity in outcomes, particularly with semaglutide, warrants further investigation.

Trial registration

PROSPERO CRD420251007882.

Clinical trial number

Not applicable.