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

This meta-analysis found no statistically significant association between GLP-1 receptor agonist use and diabetic retinopathy progression (pooled RR = 1.07, 95% CI 0.90–1.28). It reviewed 11 studies, including RCTs and retrospective cohorts, comparing several GLP-1RAs with placebo or SGLT-2 inhibitors. Semaglutide showed higher risk estimates in two studies, leading the authors to call for further investigation.

Systematic review — Systematic review and meta-analysis. Population: Patients with diabetes from RCTs and retrospective cohort studies in North America, Europe, and East Asia. Sample size: Ranging from 137 to 9,463 participants across 11 studies. Interventions: albiglutide; liraglutide; semaglutide; exenatide; dulaglutide.

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

For researchers investigating Liraglutide, this paper places liraglutide among multiple GLP-1RAs evaluated for retinal safety and reports no significant overall association with diabetic retinopathy progression. It does not establish a liraglutide-specific risk estimate or safety profile, and the semaglutide-specific signal suggests class-level conclusions may not apply uniformly to every GLP-1RA. The paper provides no dosing, duration, or clinical recommendations.

Key findings

• Pooled analysis of 11 studies found no statistically significant association between GLP-1RA use and diabetic retinopathy progression (RR = 1.07, 95% CI: 0.90–1.28).
• Semaglutide had the highest RR for diabetic retinopathy progression in two studies: RR = 1.76 (1.11–2.79) and RR = 6.41 (0.67–61.46).
• Subgroup analyses by GLP-1RA type and geographical location showed no significant differences.
• Sensitivity analyses confirmed the robustness of the findings.
• No publication bias was detected, with P > 0.05 for Egger's and Begg's tests.
• Risk of bias analysis revealed low risk across most domains.

Limitations

• Heterogeneity in outcomes, particularly with semaglutide, warrants further investigation, as stated by the authors.
• The semaglutide subgroup finding is based on only two studies, one with a very wide confidence interval.
• Inclusion of retrospective cohort studies means residual confounding cannot be excluded.
• Pooling RCTs and cohort studies across different designs, locations, and comparators may introduce clinical and methodological heterogeneity.

The record

• Journal: BMC ophthalmology
• Published: 2026-06-30
• PMID: 42380920 — DOI: 10.1186/s12886-026-05036-9
• Author countries: China, Pakistan

Peptide profiles: Liraglutide.

All indexed evidence: Liraglutide trials & papers.

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