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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. The Article Publishing Charge (APC) for this article was paid by Johns Hopkins University.

Keywords:

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

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