Semaglutide and the risk of diabetic retinopathy—current perspective
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In SUSTAIN-6, the risk of retinopathy-related complications with semaglutide 1 mg was higher for people with a history of proliferative or non-proliferative diabetic retinopathy at baseline, with higher baseline HbA1c and longer diabetes duration.
“the risk was higher for people with a history of proliferative or non-proliferative diabetic retinopathy at baseline, with higher baseline HbA1c and longer diabetes duration”
From Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? (2024) · cites this paper as [100]
In SUSTAIN-6, treatment with semaglutide 1 mg led to retinopathy-related complications in 3% of people compared with 1.8% on placebo.
“In SUSTAIN-6, treatment with semaglutide 1 mg led to the development of retinopathy-related complications in more people (3%) compared to placebo (1.8%)”
From Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? (2024) · cites this paper as [100]
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Cites
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Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity
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“Diabetic retinopathy has been a concern with semaglutide, as well as other GLP-1 RAs.79 In STEP 2, diabetic retinopathy was reported in 4.0% of patients receiving semaglutide 2.4 mg, 2.7% with semaglutide 1.0 mg, and 2.7% with placebo.39 In the SUSTAIN 6 trial, which enrolled participants with type 2 diabetes, diabeti…”
BackgroundInfluentialUsage of Glucagon-Like Peptide-1 for Obesity in Children; Updated Review of Clinicaltrials.gov
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“%) and the risk was higher for people with a history of proliferative or non-proliferative diabetic retinopathy at baseline, with higher baseline HbA1c and longer diabetes duration [99,100].”
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“…can disrupt the adaptive regulation of oxygenation in the retinal blood vessels, inhibit angiogenesis, and lead to further deterioration of the already compromised vascular endothelium in hyperglycemic conditions, potentially accelerating the progression of existing diabetic retinopathy [5–8].”
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The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe?
Kounatidis, D. C., Vallianou, N. G., Rebelos, E., Vallianou, K., Diakoumopoulou, E., Makrilakis, K., & Tentolouris, N. (2025) · Biomolecules · doi:10.3390/biom15091284 · Cited by 13 · see citing works
“Ocular safety has also emerged as a key consideration in GLP-1 RA therapy, encompassing worsening of diabetic retinopathy (DR), particularly in semaglutide users with pre-existing DR at baseline, as well as ischemic optic neuropathy (ION) [75,98,99].”
Glucagon-like peptide-1 receptor agonists: a review from a cardiovascular perspective
Turkistani, Y. (2025) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1535134 · Cited by 10 · see citing works
“Subcutaneous semaglutide should be used cautiously in patients with pre-existing diabetic retinopathy (90, 91).”
Exploring the multifaceted roles of GLP-1 receptor agonists; a comprehensive review
Hammad, B. F., Zafar, N., Ullah, M., Faisal, S. J., Iftikhar, F., Waheed, H., Muzaffar, M. W., Ahmed, K., Ashraf, F., Zahid, K., et al. (2025) · Frontiers in Clinical Diabetes and Healthcare · doi:10.3389/fcdhc.2025.1590530 · Cited by 12 · see citing works
“The results from the SUSTAIN 6 trial indicated that patients treated with semaglutide experienced a signi fi cantly higher incidence of DR compared to those receiving placebo (86).”
Huang, Y., Chen, J.-C., Li, P., Hsu, M., Cheng, C., Meyerowitz‐Katz, G., & Su, P. (2025) · Communications Medicine · doi:10.1038/s43856-025-01066-4 · Cited by 9 · see citing works
“The SUSTAIN trials reported DR worsening in some Semaglutide-treated patients, particularly those with A R D a b s o l u t e r i s k d i ff e r e n ce , RRR r e l a t i v e r i s k r e d u c t i o n , NC O s n e g a t i v e c o n t r o l o u t c o m e s . pre-existing DR 23 .”
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“Likewise with intensification of glycaemic control with Semaglutide, similar and more profound findings were reported, in the SUSTAIN trial [17, 18].”
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Use of GLP-1 Receptor Agonists for the Management of Type 1 Diabetes: A Pediatric Perspective
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“Until then, it is recommended that patients undergo screening for diabetic retinopathy before starting treatment with GLP-1 RA [105].”
Diabetic Macular Edema – Diagnostics and Treatment Guidelines
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Semaglutide Inducing Resolution of Proliferative Diabetic Retinopathy: A Case Report
Cool, D., Coventon, J., & Sharma, A. (2024) · Case Reports in Ophthalmological Medicine · doi:10.1155/crop/5834769 · Cited by 5 · see citing works
Self-citationSystemic Medications and Their Ocular Side Effects
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“29,85”
Current Treatment Options for Diabetic Retinal Disease
Bloomquist, R. F., Bloomquist, D. T., & Gardner, T. W. (2024) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2024.0548 · Cited by 4 · see citing works
“91 However, meta-analysis of randomized controlled trials failed to fi nd a causative association between semaglutide and increased DR risk.”
Optimising renal risk parameters in type 2 diabetes mellitus: Perspectives from a retinal viewpoint
Jacob, S., & Varughese, G. I. (2024) · Clinical Medicine · doi:10.1016/j.clinme.2024.100031 · Cited by 4 · see citing works
“13 It is therefore prudent to collaborate with the retinal specialist and local diabetic eye screening programme in such situations where challenging clinical scenarios warrant close observation and a more watchful approach.”
BackgroundVujosevic, 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
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“11,12 The early worsening of pre-existing DR has also been previously noted in various situations with the introduction of other treatments that has resulted in quick improvement of diabetes control.”
Demystifying the Progression of Retinopathy with Glucagon-Like Peptide-1 Receptor Agonists
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“These findings are consistent with previous studies, such as the DCCT 31 and UKPDS, 32 which demonstrated that rapid HbA1c reduction was associated with transient exacerbation of DR. 33 In contrast, the LEADER trial reported no statistically significant difference between liraglutide and placebo in the incidence of DR…”
The temporal trends in association between newer medications and diabetic retinopathy
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Utilizing Semaglutide for Addressing Type-2 Diabetes and Obesity
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Evaluating the Ocular Safety Profile of Glucagon-Like Peptide-1 Receptor AgonistsPreprint
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“Concerns were raised following an increased incidence of diabetic retinopathy with semaglutide, resulting in a trial (FOCUS) observing patients for 5-year treatment duration to assess the long-term risk [13].”
Sharma, P. K., Viswaprasad, V., Choudhary, A., Nurulhasan, A. R., Redkar, S. V., Bharatkumar, P. M., Patil, V. S., Anand, S., Barge, V. B., Shah, S. J., et al. (2026) · Metabolism Open · doi:10.1016/j.metop.2026.100476
“Although subsequent real-world data have not consistently replicated this finding, ongoing vigilance through prospective ocular assessments is warranted [17,18].”
Geroprotective Agents, Including Glucagon-Like Peptide-1 Receptor Agonists, for Ocular Health
Nguyen, A., Zhu, A., & Khouri, A. S. (2026) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1177/10807683261456222
Juran, T., Ramoin, J., Zabaneh, I. D., Shafiee, A., Newman, S., Teigen, K., & Young, R. A. (2026) · Research Square · doi:10.21203/rs.3.rs-9960273/v1
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
GLP-1 receptor agonists—a potential therapy for chronic kidney disease?
Boeckhaus, J., Sayer, J. A., & Mabillard, H. R. (2026) · Clinical Science · doi:10.1042/cs20261312
- Authors
- Sharma, A., Parachuri, N., Kumar, N., Saboo, B., Tripathi, H. N., Kuppermann, B. D., & Bandello, F.
- Affiliations
- Madhavi Netralaya (IN)
- University of California, Irvine (US)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Sharma, Ashish
- Venue
- Eye
- Published
- 2021-08-09
- Volume
- 36
- Issue
- 1
- Pages
- 10-11
- ISSN
- 0078-5334 (ISSN-L)
- 0950-222X
- 1476-5454
- PMC
- PMC8727607
- OpenAlex
- W3192887403
- Cited by
- 43
- References
- 10
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 17 · 2023: 2 · 2022: 2
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Eye (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- semaglutide, diabetic retinopathy, GLP-1 receptor agonists, type 2 diabetes, obesity, weight management, adverse drug reactions, ocular toxicity
- MeSH terms
- Semaglutide, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Glucagon-Like Peptides, Humans, Hypoglycemic Agents
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