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Semaglutide and Neovascular Age-Related Macular Degeneration among Adults with Type 2 Diabetes: An Observational Health Data Sciences and Informatics Network Study

Cai CX, Toy B, Martin B, Fan R, Westlund E, Tran D, Nishimura A, Lee H et al.

Ophthalmology, 2026

Abstract

Purpose: To investigate the potential association of semaglutide use and neovascular age-related macular degeneration (NVAMD).

Design: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics network from December 1, 2017, through December 31, 2024.

Participants: Adults with type 2 diabetes (T2D) taking semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs; e.g., dulaglutide or exenatide), or non-GLP-1RAs (e.g., empagliflozin, sitagliptin, or glipizide).

Methods: The association between semaglutide use and NVAMD was assessed using 2 approaches: an active-comparator cohort design and a self-controlled case series analysis. The former used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The latter 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) and one based on 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 that of users of dulaglutide (NVAMD-C: HR, 0.57; 95% CI, 0.21-1.57; P = 0.28; NVAMD-CP: HR, 0.25; 95% CI, 0.05-1.27; P = 0.10), empagliflozin (NVAMD-C: HR, 0.98; 95% CI, 0.54-1.79; P = 0.94; NVAMD-CP: HR, 0.79; 95% CI, 0.38-1.64;…

How strong is the evidence?

Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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