Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes – A systematic review and meta-analysis
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Aims The effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders. Methods We conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis. Results GLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05-1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00-1.43), using placebo as a comparator (1.22, 1.05-1.42). In subgroups with patients who had T2DM ≥10 years (1.19, 0.99-1.42) or with subjects enrolled from multiple countries (1.2, 0.99-1.46), the association appeared to be evident but did not reach statistical significance. Conclusions GLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted.
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In the same meta-analysis, longer treatment periods with GLP-1 RAs were associated with a greater risk of rapid worsening of diabetic retinopathy.
“with longer treatment periods associated with a greater risk [90].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [90]
A meta-analysis of 13 RCTs revealed that GLP-1 RAs, including liraglutide, semaglutide, and dulaglutide, are associated with a 23% increased risk of rapid worsening of diabetic retinopathy in T2DM (OR 1.23; 95% CI 1.05 to 1.44).
“a meta-analysis of 13 RCTs revealed that GLP-1 RAs, including liraglutide, semaglutide, and dulaglutide, are associated with a 23% increased risk of rapid worsening of diabetic retinopathy in T2DM (OR, 1.23; 95% CI 1.05 to 1.44), with longer treatment periods associated with a greater risk [90].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [90]
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Liang, L., Yu, L., He, Y., Liu, L., Yuan, H., Hu, Y., & Sun, J. (2025) · Canadian Journal of Ophthalmology · doi:10.1016/j.jcjo.2025.08.009 · Cited by 6 · see citing works
Wu, T.-E., & Chen, H.-S. (2026) · Journal of the Chinese Medical Association · doi:10.1097/jcma.0000000000001370 · Cited by 5 · see citing works
Vitreous hemorrhage during GLP-1 receptor agonist treatment
Kim, D. S., Latollari, A., & Khaimova, R. (2023) · Journal of the American Pharmacists Association · doi:10.1016/j.japh.2023.02.018 · Cited by 4 · see citing works
Are GLP-1 receptor agonists and diabetic retinopathy foes or friends?
Liu, K., Liu, S., Wang, D., & Qiao, H. (2025) · Diabetes & Metabolism · doi:10.1016/j.diabet.2025.101696 · Cited by 5 · see citing works
Goldenberg, R. (2022) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2022.108285 · Cited by 4 · see citing works
Vujosevic, S., Toma, C., Ferrulli, A., Cillà, S. D., Nucci, P., & Luzi, L. (2025) · Acta Diabetologica · doi:10.1007/s00592-025-02552-w · Cited by 3 · see citing works
Inflammatory optic neuritis and scleritis following commencement of semaglutide: a case report
Maher, C. B., Guo, B., & Dunlop, A. A. S. (2025) · Journal of Surgical Case Reports · doi:10.1093/jscr/rjaf937 · Cited by 3 · see citing works
Current and Emerging Pharmacologic Therapies for Diabetic Retinopathy
Clements, J. N., Mesawich, J., & Twisdale, C. (2026) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.70119 · Cited by 3 · see citing works
Glucose Control and Diabetic Retinopathy
Bhat, S., & Menon, A. S. (2023) · Chronicle of Diabetes Research and Practice · doi:10.4103/cdrp.cdrp_cdrp_22_22 · Cited by 2 · see citing works
Demystifying the Progression of Retinopathy with Glucagon-Like Peptide-1 Receptor Agonists
Kesavadev, J., Unnikrishnan, A. G., Sanyal, D., Aneja, P., & Saboo, B. (2022) · International Journal of Diabetes and Technology · doi:10.4103/ijdt.ijdt_17_22 · Cited by 1 · see citing works
Retinopathy, Neuropathy, and Foot Care
(2025) · American Diabetes Association eBooks · doi:10.2337/9781580408462-ch19 · Cited by 1 · see citing works
Huang, J. X. F., Wu, J., Ahmad, H., Li, J., Joshi, S., Yousaf, A., Pemminati, R., & Pemminati, S. (2026) · Cureus · doi:10.7759/cureus.103234 · Cited by 1 · see citing works
Lu, D., Li, Y., Shi, J., Yu, S., Wang, X., Liang, X., Xi, M., Wu, J., Chen, P., Huang, Q., et al. (2026) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/14703203261426211 · Cited by 1 · see citing works
The Effects of GLP-1 Receptor Agonists on Retinal Microvascular Alterations
Lampsas, S., Chardalia, G.-M., Agapitou, C., Papastamopoulos, K., Theodossiadis, P., Siasos, G., Oikonomou, E., Lambadiari, V., & Chatziralli, I. (2026) · Biomedicines · doi:10.3390/biomedicines14051057 · Cited by 2 · see citing works
Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis
Al-Burak, S. A., Voznyy, V., Elganga, M., Zajner, C., Juncal, V., Sheidow, T., & Malvankar‐Mehta, M. S. (2026) · Canadian Journal of Ophthalmology · doi:10.1016/j.jcjo.2026.05.004 · Cited by 1 · see citing works
Ortiz-Seller, A., Real, J. T., Morcillo, E. J., & Ortiz, J. L. (2026) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2026.08.007 · Cited by 1 · see citing works
Landgraf, R., Aberle, J., Birkenfeld, A. L., Gallwitz, B., Kellerer, M., Klein, H. H., Müller‐Wieland, D., Nauck, M. A., Wiesner, T., & Siegel, E. G. (2024) · Die Diabetologie · doi:10.1007/s11428-023-01144-y · Cited by 1 · see citing works
Konservative Adipositastherapie
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Król, M., Żychowska, J., Łagowski, R., Kupnicka, P., Simińska, D., & Chlubek, D. (2023) · Pomeranian Journal of Life Sciences · doi:10.21164/pomjlifesci.965
Buckley, A. J., Tan, G. D., Gruszka-Goh, M. H., Scanlon, P. H., Ansari, I., & Suliman, S. G. I. (2025) · Diabetologia · doi:10.1007/s00125-025-06562-9
Glucagon-Like Peptide-1 Receptor Agonists
Whitley, H. P. (2025) · American Diabetes Association eBooks · doi:10.2337/9781580408462-ch13
Evaluating the Ocular Safety Profile of Glucagon-Like Peptide-1 Receptor AgonistsPreprint
Khan, Z., Chaudhry, F. W., Dhar, N., & Adyanthaya, R. S. (2025) · Research Square · doi:10.21203/rs.3.rs-8371495/v1
Vitreous hemorrhage after weight loss therapy
Al-Hinai, A. (2026) · Oman Journal of Ophthalmology · doi:10.4103/ojo.ojo_60_26
Maideen, N. M. P., Rashid, S. A., Balasubramanian, R., & Amirthalingam, P. (2026) · Indian Journal of Ophthalmology · doi:10.4103/ijo.ijo_2659_25
Chen, K.-E., Wang, P.-C., Lin, H., & Lin, S. J. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.70744
Akande, R. O., & Albert, S. G. (2026) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2026.113429
GLP-1 receptor agonists in diabetes-associated neurological disorders
Rasooli, R., Sharifzadeh, M., Rassouli, A., & Bekheir, S. A. (2026) · Brain Disorders · doi:10.1016/j.dscb.2026.100326
The Dark Side of GLP-1 Receptor Agonists: Risks and Adverse Events
Nawal, C. L., Saini, H. L., Rankawat, G., & Chejara, R. S. (2026) · Journal of the Association of Physicians of India · doi:10.59556/japi.74.1655
The eye in the era of GLP-1 receptor agonists ‒ a narrative review of current evidence
Rusinek, H., Korniluk, J., Milusz, N., Dmoch, W., & Maciejewicz, P. (2026) · European Journal of Clinical and Experimental Medicine · doi:10.15584/ejcem.2026.3.8
- Authors
- Yoshida, Y., Joshi, P., Barri, S., Wang, J., Corder, A. L., O'Connell, S. S., & Fonseca, V. A.
- Affiliations
- Tulane University (US)
- Corresponding author
- Yoshida, Yilin
- Fonseca, Vivian A.
- Venue
- Journal of Diabetes and its Complications
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 36
- Issue
- 8
- Pages
- 108255
- ISSN
- 0891-6632 (ISSN-L)
- 1056-8727
- OpenAlex
- W4283816664
- Cited by
- 65
- References
- 49
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 19 · 2023: 11 · 2022: 3
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 368 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Journal of Diabetes and its Complications (acceptedVersion)
- PubMed (publishedVersion)
- 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, type 2 diabetes, liraglutide, semaglutide, dulaglutide, retinopathy progression, cardiovascular benefits, adverse effects
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Humans, Hypoglycemic Agents
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