Analysis of 810,000+ semaglutide users across 14 databases found no increased risk of serious diabetic eye disease compared to other diabetes medications.
810,390 patients, no increased riskThe largest real-world study of semaglutide and diabetic eye disease found no increased retinopathy risk across 14 databases
What the researchers found
In the largest real-world study of its kind — analyzing over 810,000 new semaglutide users across 14 databases — semaglutide showed no increased risk of proliferative diabetic retinopathy (PDR) or treatment-requiring diabetic eye disease compared to other GLP-1 drugs or non-GLP-1 diabetes medications.
Semaglutide's risk of PDR was similar to dulaglutide (HR 0.81), empagliflozin (HR 0.83), and sitagliptin (HR 0.83), and significantly lower than glipizide (HR 0.59, p=0.01). For treatment-requiring retinopathy/macular edema, semaglutide actually showed lower risk than dulaglutide (HR 0.53, p=0.02), sitagliptin (HR 0.46, p=0.008), and glipizide (HR 0.55, p=0.02).
These findings provide strong reassurance that the retinopathy signal seen in the earlier SUSTAIN 6 trial does not translate into increased real-world eye disease risk.
Why it matters
The SUSTAIN 6 trial flagged a potential link between semaglutide and diabetic eye complications, creating concern among clinicians and patients. This massive real-world study — covering 810,000+ patients across 14 databases — provides the most definitive evidence to date that semaglutide does not increase retinopathy risk. In fact, it may lower the risk compared to several other diabetes drugs.
The numbers in context
n=810,390 semaglutide users · 14 databases · PDR vs dulaglutide: HR 0.81, p=0.51 · PDR vs glipizide: HR 0.59, p=0.01 · DR/DME vs sitagliptin: HR 0.46, p=0.008 · 2017–2023
How the study worked
Retrospective cohort study using 14 databases (6 administrative claims, 8 electronic health records) in the OHDSI Evidence Network. New semaglutide users for type 2 diabetes were compared to users of other GLP-1 drugs (dulaglutide, exenatide) and non-GLP-1 drugs (empagliflozin, sitagliptin, glipizide) using propensity score-adjusted Cox proportional hazards models. Network-wide estimates were generated via random-effects meta-analysis.
Who was studied
810,390 adults with type 2 diabetes who were new users of semaglutide across 14 healthcare databases in the US (December 2017–December 2023)
What this study cannot tell us
This is a retrospective observational study, not a randomized trial, so residual confounding is possible despite propensity score adjustment. Claims and EHR data may have coding inaccuracies for eye disease diagnoses. The study period (2017–2023) may not capture very long-term effects. Patients with pre-existing severe retinopathy may have been less likely to be prescribed semaglutide, potentially biasing results.
How to read the evidence
This is a large-scale retrospective cohort study using propensity score adjustment across 14 independent databases with random-effects meta-analysis. The massive sample size, multiple comparator groups, and network-wide design provide strong evidence, though it remains observational rather than randomized.
When this study was published
Published in 2025 using data through December 2023, this is one of the most current and comprehensive analyses of semaglutide's retinopathy safety profile available.
The bigger picture
This study is a landmark in resolving one of the most debated safety questions about GLP-1 drugs. By leveraging the massive OHDSI network, it provides population-level evidence that semaglutide's early clinical trial retinopathy signal does not translate into real-world harm. This should give clinicians greater confidence in prescribing semaglutide to patients with type 2 diabetes, including those at risk for eye disease.
Questions still open
- Does the apparent protective effect of semaglutide on diabetic eye disease hold up in longer follow-up periods?
- Are the lower retinopathy rates with semaglutide driven by better overall glycemic control or by a direct protective mechanism?
- Do newer multi-agonist drugs like tirzepatide and retatrutide show similar retinopathy safety profiles?
Common questions
Does semaglutide cause diabetic eye problems?
Should I still get eye exams while taking semaglutide?
Read the original research
Semaglutide and diabetic retinopathy: an OHDSI network study.
BMJ open diabetes research & care, 13(6)
Citation
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. (2025). Semaglutide and diabetic retinopathy: an OHDSI network study.. BMJ open diabetes research & care, 13(6). https://doi.org/10.1136/bmjdrc-2025-005424