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Semaglutide and Neovascular Age-Related Macular Degeneration among Adults with Type 2 Diabetes: An Observational

Cindy X Cai¹, Brian Toy², Benjamin Martin³

¹Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland; Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

|June 2, 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; P = 0.52), sitagliptin (NVAMD-C: HR, 2.08; 95% CI, 0.90-4.83; P = 0.09; NVAMD-CP: HR, 1.80; 95% CI, 0.55-5.86; P = 0.33), and glipizide (NVAMD-C: HR, 0.83; 95% CI, 0.35-2.02; P = 0.69; NVAMD-CP: HR, 0.50; 95% CI, 0.21-1.19; P = 0.12). No evidence was found of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: IRR, 0.92; 95% CI, 0.67-1.26; P = 0.60; NVAMD-CP: IRR, 1.02; 95% CI, 0.76-1.36; P = 0.92) nor with any of the other GLP-1RAs or non-GLP-1RAs.

Conclusions:

We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D.

Financial Disclosure(S):

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords:

Big data Neovascular age-related macular degeneration Observational Health Data Sciences and Informatics Semaglutide

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