Semaglutide and Neovascular Age-Related Macular Degeneration Among Adults with Type 2 Diabetes: An OHDSI Network Study.

OBJECTIVE: or Purpose: To investigate the potential association of semaglutide and neovascular age-related macular degeneration (NVAMD) DESIGN: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network during the study period from 12/1/2017-12/31/2024 SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Adults with type 2 diabetes (T2D) on semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs) (dulaglutide, exenatide), or non-GLP-1RAs (empagliflozin, sitagliptin, glipizide) METHODS, INTERVENTION OR TESTING: The association between semaglutide and NVAMD was assessed using two approaches: an active-comparator cohort design and a self-controlled case-series (SCCS) analysis. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). A random-effects meta-analysis was used to generate network-wide HR and IRR estimates. MAIN OUTCOME MEASURES: Two definitions of NVAMD, one based on condition codes alone (NVAMD-C) or condition codes and procedures (NVAMD-CP). RESULTS: A total of 227,971 new users of semaglutide were included in the study. The risk of NVAMD among semaglutide users was similar to users of dulaglutide (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), empagliflozin (NVAMD-C HR 0.98, 95% CI 0.54 to 1.79, P=.94; NVAMD-CP HR 0.79, 95% CI 0.38 to 1.64, P=.52), sitagliptin (NVAMD-C HR 2.08, 95% CI 0.90 to 4.83, P=.09; NVAMD-CP HR 1.80, 95% CI 0.55 to 5.86, P=.33), and glipizide (NVAMD-C HR 0.83, 95% CI 0.35 to 2.02, P=0.69; NVAMD-CP HR 0.50, 95% CI 0.21 to 1.19, P=.12). There was no evidence of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: incidence rate ratio [IRR] 0.92, 95% CI 0.67 to 1.26, P=.60; NVAMD-CP IRR 1.02, 95% CI 0.76 to 1.36, P=.92) nor any of the other GLP-1RA or non-GLP-1RAs. CONCLUSIONS: We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D.