The Effect of Glucagon-Like Peptide-1 Receptor Agonists on Diabetic Retinopathy at a Tertiary Care Center
Open accessAbstract
Objective: The potential association between diabetic retinopathy (DR) worsening and glucagon-like peptide-1 receptor agonists (GLP-1RA) has affected therapeutic management of diabetic patients but remains controversial. This study compared rates of DR development or progression in patients on GLP-1RA to those on SGLT-2 inhibitors (SGLT-2I). Design: Retrospective cohort study. Subjects: Nine hundred eighty-one patients with diabetes mellitus taking GLP-1RA or SGLT-2I, the latter serving as controls, between 2012 and 2023. Methods: Patients were one-to-one greedy matched by propensity scores on race/ethnicity, age, smoking status, baseline body mass index and hemoglobin A1c %, type of diabetes mellitus, baseline DR status and history of DR procedures, duration of drug use, whether they had taken both drug types, and change in hemoglobin A1c % after 1 year on the drug. Main Outcome Measures: The primary outcome was clinical DR development or progression (termed "worsening") detected by International Classification of Diseases (ICD), 10th edition codes, confirmed by manual review, on GLP-1RA compared with SGLT-2I after propensity score matching. Secondary outcomes included DR worsening indicated by need for procedures due to complications, and time-to-first DR worsening event. Results: The study included 692 GLP-1RA users and 289 SGLT-2I users. The mean follow-up periods for GLP-1RA versus SGLT-2I use were 1.54 (standard deviation [SD] 1.82) years and 1.38 (SD 1.56) years, respectively. The rates of clinical worsening were 2.3% and 2.8%, respectively. After propensity score matching, an association was not identified between GLP1-RA and DR worsening neither clinically by ICD-10 codes (odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.11-1.03) nor by indication for procedures (OR = 0.50, 95% CI 0.13-2.00). Time-to-first DR worsening did not differ between the groups in Kaplan-Meier analysis. The most common type of clinical worsening event for both drug types was vitreous hemorrhage (43.7% and 50% of worsening events in GLP-1RA and SGLT-2I users, respectively). The most common DR procedure indicated was anti-VEGF injections (34% and 35% of GLP-1RA and SGLT-2I events, respectively). Conclusions: Diabetic retinopathy worsening, either clinically or by procedures, was not associated with GLP-1RA compared with SGLT-2I, both before and after propensity score matching on all analyses, including time-to-first worsening event. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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A retrospective study with 981 patients with T2DM showed no difference in diabetic retinopathy progression between GLP-1 RAs and SGLT-2 inhibitors.
“Conversely, a retrospective study with 981 patients with T2DM showed no difference in diabetic retinopathy progression between GLP-1 RAs and SGLT-2 inhibitors [94].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [94]
The Abstract Results report 692 GLP-1RA users and 289 SGLT-2I users (981 total), and the Results report no significant difference in diabetic retinopathy worsening between the groups. However, Table 1 shows that only 905 participants had T2DM; the other 76 had T1DM. The claim incorrectly describes all 981 as patients with T2DM. (LLM, conf=0.92)
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Wu, B., & He, B. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.71490
- Authors
- Joo, J. H., Sharma, N., Shaia, J., Wu, A. K., Skugor, M., Singh, R. P., & Rachitskaya, A. V.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Rachitskaya, Aleksandra V.
- Venue
- Ophthalmology Science
- Publisher
- Elsevier BV
- Published
- 2024-11
- Volume
- 4
- Issue
- 6
- Pages
- 100547
- ISSN
- 2666-9145 (ISSN-L)
- PMC
- PMC11321299
- OpenAlex
- W4396668954
- Cited by
- 37
- References
- 46
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 2
- FWCI
- 12.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Ophthalmology Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Research to Prevent Blindness (P30-EY025585)
- Biogen
- F. Hoffmann-La Roche
- Cleveland Clinic (P30EY025585)
- Regeneron Pharmaceuticals
- Alimera Sciences
- Apellis Pharmaceuticals
- Novo Nordisk
- U.S. Food and Drug Administration
- Genentech
- Allergan
- National Eye Institute (P30EY025585, T32EY024236)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- GLP-1 receptor agonists, diabetic retinopathy, SGLT2 inhibitors, diabetic retinopathy progression, vitreous hemorrhage, diabetic macular edema, diabetic cataract, diabetic retinopathy surgery, diabetes mellitus, drug safety, propensity score matching, HbA1c, glycemic control
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