Semaglutide shows no increased or decreased neovascular age-related macular degeneration risk in Type 2 Diabetes

Neovascular age-related macular degeneration (NVAMD) is a leading cause of severe vision loss, particularly prevalent in older adults and those with Type 2 Diabetes (T2D). While GLP-1 receptor agonists (GLP-1RAs) like semaglutide are highly effective for T2D management, recent pharmacovigilance reports have raised concerns about potential ocular adverse events, including nonarteritic anterior ischemic optic neuropathy (NAION). This study aimed to specifically investigate whether semaglutide, a widely used GLP-1RA, is associated with an increased or decreased risk of NVAMD in the T2D population, addressing a critical safety question.

Researchers conducted a retrospective study across 12 databases within the Observational Health Data Sciences and Informatics (OHDSI) network, analyzing data from December 1, 2017, to December 31, 2024. The study included 227,971 new users of semaglutide with Type 2 Diabetes. Comparator groups included other GLP-1RAs (dulaglutide, exenatide) and non-GLP-1RAs (empagliflozin, sitagliptin, glipizide). The association between semaglutide and NVAMD was assessed using two robust approaches: an active-comparator cohort design with propensity score-adjusted Cox proportional hazards models and a self-controlled case-series (SCCS) analysis using conditional Poisson regression models. A random-effects meta-analysis generated network-wide estimates for hazard ratios (HRs) and incidence rate ratios (IRRs).

The study found no statistically significant evidence of an increased or decreased risk of neovascular age-related macular degeneration (NVAMD) associated with semaglutide exposure. When compared to dulaglutide, semaglutide users showed similar NVAMD risk (NVAMD-C HR 0.57, 95% CI 0.21 to 1.57, p=.28; NVAMD-CP HR 0.25, 95% CI 0.05 to 1.27, p=.10). Similar non-significant findings were observed against empagliflozin (NVAMD-C HR 0.98, p=.94; NVAMD-CP HR 0.79, p=.52), sitagliptin (NVAMD-C HR 2.08, p=.09; NVAMD-CP HR 1.80, p=.33), and glipizide (NVAMD-C HR 0.83, p=0.69; NVAMD-CP HR 0.50, p=.12). The self-controlled case-series analysis further supported these findings:

For semaglutide exposure, the incidence rate ratio for NVAMD-C was 0.92 (95% CI 0.67 to 1.26, p=.60), and for NVAMD-CP it was 1.02 (95% CI 0.76 to 1.36, p=.92), indicating no significant association.