Impact of glucagon‐like peptide‐1 receptor agonists on diabetic retinopathy: A meta‐analysis of clinical studies emphasising retinal changes as a primary outcome

Abstract Background To determine if glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are associated with the development and progression of diabetic retinopathy (DR). Methods A systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP‐1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta‐analysis was pooled using a random‐effects model. Results Analysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP‐1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP‐1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01). Conclusion Our findings indicate no elevated risk of incidence of DR linked to GLP‐1RA compared to insulin. In fact, GLP‐1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP‐1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c – a phenomenon not specific to GLP‐1RA and warrants further investigation.