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

“Semaglutide and Neovascular Age-Related Macular Degeneration Among Adults with Type 2 Diabetes: An OHDSI Network Study. Cai CX(1), Toy B(2), Martin B(3), Fan R(4), Westlund E(5), Tran D(6), Nishimura A(5), Lee H(3), Leng T(7), Nagy P(3), Mathioudakis N(8), Zhang L(4), Hribar M(9), Chen A(10), Armbrust K(11), Goetz K(12), Baxter S(13), Boland MV(14), Brown EN(15), Tsui E(16), Barkmeier AJ(17), Wang S(7), Mehta N(18), Stocking JC(19), O'Keefe G, Lee CS(20), Payne PRO(4), O'Brien WJ(21), DuVall S(22), Alshammari T(23), Falconer T(24), Dorr DA(25), Humes I(26), McCoy D(26), Adibuzzaman M(26), Mahmood R(26), Morgan-Cooper H(27), Desai P(27), Kothari SY(27), Sena A(28), Blacketer C(28), Ostropolets A(29), Shoaibi A(30), Rao G(31), Hripcsak G(24), Ryan P(32), Suchard MA(33). Author information: (1)Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA, Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: ccai6@jhmi.edu. (2)Roski Eye Institute, Keck School of Medicine, University of Southern California; Los Anglees, CA. (3)Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (4)Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St. Louis, St. Louis, MO. (5)Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. (6)Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. (7)Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, CA. (8)Department of Medicine, Johns Hopkins University School of Medicine. (9)Ophthalmology and Visual Sciences, AI.Health4All College of Medicine, University of Illinois at Chicago, Chicago, IL USA. (10)Casey Eye Institute, Oregon Health & Science University, Portland, OR, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR. (11)Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN Department of Ophthalmology, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota. (12)Topcon Healthcare, Inc. Oakland, NJ. (13)Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA. (14)Department of Ophthalmology, Mass Eye and Ear and Harvard Medical School; Boston, MA. (15)Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, USA. (16)UCLA Stein Eye Institute, Los Angeles, CA. (17)Mayo Clinic, Department of Ophthalmology, Rochester, MN. (18)Department of Ophthalmology, NYU Langone Health, New York, NY. (19)Department of Internal Medicine, University of California Davis, Sacramento, CA. (20)John F. Hardesty MS Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, MO. (21)Veterans Affairs Informatics and Computing Infrastructure, Salt Lake City, UT. (22)PurpleLab, Inc., Salt Lake City, UT; Conflicts of Interest: Employee and Shareholder of PurpleLab. (23)Department of Clinical Practice, College of Pharmacy, Jazan University, Jazan, Saudi Arabia Pharmacy Practice Research Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia. (24)Department of Biomedical Informatics, Columbia University, New York, NY. (25)Division of Informatics, Clinical Epidemiology, and Translational Data Science, Department of Medicine, Oregon Health & Science University, Portland, OR. (26)Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA. (27)Stanford School of Medicine and Stanford Health Care, Palo Alto, CA, United States. (28)Johnson & Johnson, Raritan, NJ USA Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands. (29)Department of Biomedical Informatics, Columbia University, New York, NY; Johnson & Johnson, Raritan, NJ USA. (30)Johnson & Johnson, Raritan, NJ USA. (31)CoReason, INC. (32)Department of Biomedical Informatics, Columbia University, New York, NY Johnson & Johnson, Raritan, NJ USA. (33)Department of Biostatistics, UCLA School of Public Health, University of California, Los Angeles VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, UT. 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. Copyright © 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved.”