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Home For Prescribers Diabetic retinopathy early worsening with rapid A1c drops

Diabetic retinopathy early worsening with rapid A1c drops

Semaglutide, SUSTAIN-6, and retinal monitoring

Reviewed by Dr. James Deom, OD, MPH, FAAO, FSLS, Chief of Eye Care Services, Hazleton Eye Specialists Last reviewed: November 12, 2026 Audience: Prescribers

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The short version

  • Early worsening of diabetic retinopathy after rapid, large improvement in glucose control is a long-recognized phenomenon, documented with intensive insulin therapy in the DCCT.¹
  • In SUSTAIN-6, semaglutide was associated with a higher rate of retinopathy complications than placebo.² A post hoc analysis attributed most of that difference to the size and speed of the early A1c drop in patients with pre-existing retinopathy and poor baseline control, many on insulin.³
  • The AAO (November 2026) recommends an initial period of increased retinopathy monitoring for patients with diabetes starting a GLP-1 RA, especially if baseline A1c has been poorly controlled. It describes evidence that GLP-1 RAs themselves worsen retinopathy as mixed and not conclusive.⁴
  • Semaglutide labeling for diabetes includes a warning on diabetic retinopathy complications.⁵
  • The long-term glycemic benefit for retinopathy is well established. The aim is closer monitoring, not avoiding effective treatment.¹

What the trials showed

DCCT (type 1 diabetes, intensive insulin). Early worsening at 6 and/or 12 months occurred in 13.1% of intensively treated patients versus 7.6% with conventional treatment. About half recovered by 18 months, and the long-term benefit of intensive control outweighed the early risk. Higher screening A1c and the size of the reduction in the first 6 months were the main risk factors.¹

SUSTAIN-6 (type 2 diabetes, semaglutide 0.5 or 1.0 mg weekly vs placebo, 104 weeks). Retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring intravitreal treatment or photocoagulation) were significantly more frequent with semaglutide: 3.0% vs 1.8% (HR 1.76, 95% CI 1.11–2.78).²

Prescribing information. The Ozempic label (section 5.3) reports the same 3.0% vs 1.8% difference and notes that the absolute risk increase was larger in patients with a history of diabetic retinopathy at baseline (8.2% vs 5.2%) than in those without (0.7% vs 0.4%). It states that rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy, that the effect of long-term glycemic control with semaglutide on retinopathy complications has not been studied, and that patients with a history of retinopathy should be monitored.⁵

Post hoc SUSTAIN analysis. There was no imbalance in retinopathy adverse events in SUSTAIN 1 to 5. In SUSTAIN-6, most of the effect was associated with the magnitude and rapidity of A1c reduction during the first 16 weeks in patients with pre-existing retinopathy, poor baseline control, and insulin treatment, consistent with early worsening.³

Who to watch most closely

  • Known diabetic retinopathy, particularly moderate or worse NPDR, PDR, or diabetic macular edema
  • High baseline A1c with an expected large, rapid reduction
  • Long diabetes duration, insulin use
  • No dilated eye exam in the past 12 months

Suggested approach

  1. Before starting (or as soon as possible), confirm a dilated retinal exam within the past 12 months; arrange one if not, especially for patients in the groups above.
  2. During titration, consider a more gradual A1c reduction in patients with significant retinopathy, in consultation with eye care, and arrange earlier retinal follow-up.⁴
  3. Tell patients to report new blurred vision, floaters, or vision loss promptly. Sudden vision loss needs same-day care.
  4. Share findings both ways: send A1c trends and the GLP-1 RA start date to eye care; we will send retinopathy staging and the recommended interval back.

Dr. Deom’s recommendation (clinical opinion / practice recommendation)

Dr. James Deom recommends that everyone starting or taking a GLP-1 medication have a comprehensive dilated eye exam with OCT, OCT angiography (OCTA), and retinal photography (fundus photos with autofluorescence) as a baseline and for follow-up, and seek same-day care for sudden vision loss.

This is his clinical opinion and practice recommendation, not a society mandate. AAO and NANOS do not recommend routine examination solely to predict NAION, and no exam or imaging test reliably predicts or prevents an acute event. The baseline is intended to document disc anatomy and retinal status for later comparison and to detect other eye disease. See the study comparison for where professional positions agree and differ.

Dr. James Deom’s personal clinical thought

This is his opinion, not established evidence. It is not a finding from the studies or a position of the FDA, EMA, AAO, NANOS, or AOA.

As patients lose weight and their overall health improves on GLP-1 medicines, blood pressure and cholesterol medicines are often not re-addressed. Over-treatment of blood pressure may lead to hypotension, which can worsen at night and could cause nighttime hypoperfusion of the optic nerve. That sequence would fit the typical presentation of NAION (vision loss noticed on waking).

He recommends that people on GLP-1 medicines also improve exercise and diet, and keep regular visits with their usual doctors, even if that clinician did not prescribe the GLP-1, so the rest of their care, including blood pressure, is maintained.

For prescribers: consider reviewing antihypertensive dosing and timing (including bedtime dosing) as weight drops. Coordinate changes with the patient’s usual clinician when someone else wrote the GLP-1 prescription.

How to reach us

Same-day evaluation: providers can call the office at 570-453-2020 (fax 570-453-1020), or refer a patient or ask a question by email. Patients can schedule an exam online.

For privacy, please don’t include patient names or other identifying details in email. Our team will call to schedule and gather details securely.

General contact and referrals: Hazleton Eye Specialists, phone 570-453-2020, fax 570-453-1020. See Referral information for what to send.

References

  1. Diabetes Control and Complications Trial Research Group. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol. 1998;116(7):874-886. https://pubmed.ncbi.nlm.nih.gov/9682700/
  2. Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). N Engl J Med. 2016;375(19):1834-1844. https://pubmed.ncbi.nlm.nih.gov/27633186/
  3. Vilsbøll T, et al. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab. 2018;20(4):889-897. https://pubmed.ncbi.nlm.nih.gov/29178519/
  4. American Academy of Ophthalmology. Glucagon-Like Peptide-1 Receptor Agonists and Diabetic Retinopathy: A Statement from the American Academy of Ophthalmology. November 2026. https://www.aao.org/education/clinical-statement/glucagon-like-peptide-1-receptor-agonists-diabetic
  5. Ozempic (semaglutide) injection, US Prescribing Information, Warnings and Precautions: Diabetic Retinopathy Complications. Novo Nordisk. https://www.novo-pi.com/ozempic.pdf

Medical disclaimer. This page is educational and is intended for licensed health care professionals. It is not a clinical practice guideline and does not replace clinical judgment, product labeling, or specialty consultation. Information is current as of the “last reviewed” date.