Semaglutide and diabetic retinopathy: an OHDSI network study

IntroductionSemaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes mellitus (T2D), has potential associations with higher rates of diabetic retinopathy (DR) complications including proliferative DR (PDR) and diabetic macular edema (DME). The purpose of this s...

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Published in:	BMJ open diabetes research & care Vol. 13; no. 6; p. e005424
Main Authors:	Cai, Cindy Xinji, Nishimura, Akihiko, Baxter, Sally, Goetz, Kerry, Hribar, Michelle, Toy, Brian, Barkmeier, Andrew, Wang, Sophia, Swaminathan, Swarup, Flowers, Alexis, Brown, Eric, Xu, Benjamin, Chen, John, Chen, Aiyin, Leng, Theodore, Boland, Michael, Alshammari, Thamir, Bu, Fan, Falconer, Thomas, Martin, Benjamin, Westlund, Erik, Mathioudakis, Nestoras, Zhang, Linying, Fan, Ruochong, Wilcox, Adam, Lai, Albert, Stocking, Jacqueline C, Xie, Yangyiran, Lee, Lok Hin, Dorr, David, Humes, Izabelle, McCoy, David, Adibuzzaman, Mohammad, Areaux, Raymond, Brash, James, Weiskopf, Nicole, Morgan-Cooper, Hannah, Desai, Priya, Tran, Diep, Rustam, Zainab, Zhu, Gina, Swerdel, Joel, Sena, Anthony, Nagy, Paul, Suchard, Marc, Schuemie, Martijn, Hripcsak, George, Ryan, Patrick
Format:	Journal Article
Language:	English
Published:	England American Diabetes Association 04.11.2025 BMJ Publishing Group LTD BMJ Publishing Group
Subjects:	Aged Clinical medicine Clinical trials Diabetes Diabetes Complications Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetic Retinopathy Diabetic Retinopathy - chemically induced Diabetic Retinopathy - epidemiology Epidemiology/Health services research FDA approval Female Follow-Up Studies GLP-1 receptor agonists Glucagon Glucagon-Like Peptide 1 Glucagon-Like Peptide-1 Receptor Agonists Glucagon-Like Peptides - adverse effects Glucagon-Like Peptides - analogs & derivatives Glucagon-Like Peptides - therapeutic use Hispanic Americans Humans Hypoglycemic Agents - adverse effects Hypoglycemic Agents - therapeutic use Informatics Male Middle Aged Peptides Retrospective Studies Sensitivity analysis Diabetes Complications Diabetic Retinopathy
ISSN:	2052-4897, 2052-4897
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Summary:	IntroductionSemaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes mellitus (T2D), has potential associations with higher rates of diabetic retinopathy (DR) complications including proliferative DR (PDR) and diabetic macular edema (DME). The purpose of this study was to determine whether an association exists between semaglutide and PDR and treatment-requiring DR/DME.Research design and methodsThis was a retrospective cohort study of 14 databases (six administrative claims and eight electronic health records) in the Observational Health Data Sciences and Informatics Evidence Network. Adults with T2D on semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from 1 December 2017 to 31 December 2023 were included. The association between semaglutide and PDR or treatment-requiring DR/DME was assessed using an active-comparator cohort design comparing new users of semaglutide as second-line T2D treatment to those on other GLP-1RAs and non-GLP-1RAs. Propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs). Network-wide HR estimates were generated using a random-effects meta-analysis.ResultsThe study included 810 390 new semaglutide users for T2D. PDR risk for semaglutide was similar to dulaglutide (HR 0.81, 95% CI 0.42 to 1.54, p=0.51), empagliflozin (HR 0.83, 95% CI 0.53 to 1.30, p=0.41) and sitagliptin (HR 0.83, 95% CI 0.45 to 1.55, p=0.57) but was lower than glipizide (HR 0.59, 95% CI 0.39 to 0.88, p=0.01). The risk for treatment-requiring DR/DME for semaglutide was similar to empagliflozin (HR 0.66, 95% CI 0.43 to 1.02, p=0.06) but lower than dulaglutide (HR 0.53, 95% CI 0.31 to 0.91, p=0.02), sitagliptin (HR 0.46, 95% CI 0.26 to 0.81, p=0.008) and glipizide (HR 0.55, 95% CI 0.33 to 0.91, p=0.02).Conclusions and relevanceWe did not identify increased risk for either PDR or treatment-requiring DR/DME comparing semaglutide with other GLP-1RAs or non-GLP-1RAs. Patients with T2D should still undergo close eye care follow-up, particularly when initiating new antihyperglycemic medications.
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ISSN:	2052-4897 2052-4897
DOI:	10.1136/bmjdrc-2025-005424