TY - JOUR
T1 - Semaglutide and diabetic retinopathy
T2 - an OHDSI network study
AU - Cai, Cindy Xinji
AU - Nishimura, Akihiko
AU - Baxter, Sally
AU - Goetz, Kerry
AU - Hribar, Michelle
AU - Toy, Brian
AU - Barkmeier, Andrew
AU - Wang, Sophia
AU - Swaminathan, Swarup
AU - Flowers, Alexis
AU - Brown, Eric
AU - Xu, Benjamin
AU - Chen, John
AU - Chen, Aiyin
AU - Leng, Theodore
AU - Boland, Michael
AU - Alshammari, Thamir
AU - Bu, Fan
AU - Falconer, Thomas
AU - Martin, Benjamin
AU - Westlund, Erik
AU - Mathioudakis, Nestoras
AU - Zhang, Linying
AU - Fan, Ruochong
AU - Wilcox, Adam
AU - Lai, Albert
AU - Stocking, Jacqueline C.
AU - Xie, Yangyiran
AU - Lee, Lok Hin
AU - Dorr, David
AU - Humes, Izabelle
AU - McCoy, David
AU - Adibuzzaman, Mohammad
AU - Areaux, Raymond
AU - Brash, James
AU - Weiskopf, Nicole
AU - Morgan-Cooper, Hannah
AU - Desai, Priya
AU - Tran, Diep
AU - Rustam, Zainab
AU - Zhu, Gina
AU - Swerdel, Joel
AU - Sena, Anthony
AU - Nagy, Paul
AU - Suchard, Marc
AU - Schuemie, Martijn
AU - Hripcsak, George
AU - Ryan, Patrick
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
PY - 2025/11/4
Y1 - 2025/11/4
N2 - Introduction:Semaglutide, 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 methods: This 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. Results: The study included 810390 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 relevance: We 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.
AB - Introduction:Semaglutide, 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 methods: This 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. Results: The study included 810390 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 relevance: We 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.
UR - https://www.scopus.com/pages/publications/105020993397
U2 - 10.1136/bmjdrc-2025-005424
DO - 10.1136/bmjdrc-2025-005424
M3 - Article
C2 - 41192935
AN - SCOPUS:105020993397
SN - 2052-4897
VL - 13
JO - BMJ Open Diabetes Research and Care
JF - BMJ Open Diabetes Research and Care
IS - 6
M1 - e005424
ER -
