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Does Liraglutide Worsen Diabetic Eye Disease? A Study of 181 Saudi Patients Says No

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The takeaway

In 181 Saudi patients with type 2 diabetes treated with liraglutide for a median of 2 years, most showed no worsening of retinopathy, with 25.5% of those with existing eye disease actually improving.

81.6% stayed retinopathy-free

Among patients without diabetic retinopathy at baseline, the vast majority remained retinopathy-free after a median 2 years on liraglutide, and a quarter of those with existing retinopathy improved

What the researchers found

After a median 2-year follow-up of 181 patients on liraglutide:

• 81.6% of patients (71/87) without retinopathy at baseline remained retinopathy-free

• Among patients with retinopathy at baseline: 25.5% improved, 44.7% showed no change

• Both HbA1c and weight decreased significantly (P<0.001)

• Independent risk factors for retinopathy were: insulin use (OR 2.68), hypertension (OR 2.56), higher HbA1c (OR 1.17 per unit), older age (OR 1.03 per year), and longer diabetes duration (OR 1.04 per year)

• Liraglutide itself was not identified as a retinopathy risk factor

Baseline characteristics: mean age 58.2 years, 72.9% female, median diabetes duration 19 years, median baseline HbA1c 9%, 69.6% on insulin.

Why it matters

Semaglutide's SUSTAIN-6 trial raised alarm when it showed increased retinopathy events, creating concern about the entire GLP-1 drug class. This study provides real-world data from the Middle East — a region with high diabetes prevalence — showing liraglutide does not appear to worsen retinopathy. This is particularly important for clinicians in regions where diabetes is common and retinopathy screening may be less accessible.

How the study worked

Retrospective cohort study at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Included patients aged ≥14 years with type 2 diabetes treated with liraglutide between 2015 and 2021 who had documented retinopathy assessments at baseline and follow-up. Data collected included demographics, retinopathy status, BMI, and HbA1c at baseline and follow-up. Multivariate binary mixed effect analysis was used to identify retinopathy risk factors.

What this study cannot tell us

Retrospective design without a control group limits causal conclusions. The study was conducted at a single center in Saudi Arabia, limiting generalizability. Retinopathy assessment methods and frequency were not standardized. The median baseline HbA1c of 9% indicates poorly controlled diabetes, which may not represent the broader liraglutide-treated population. Relatively small sample size (181 patients) limits power to detect small retinopathy risks.

How to read the evidence

This is a single-center retrospective cohort study without a control group. While it provides useful real-world safety data, the lack of a comparator group and non-standardized assessments limit the strength of conclusions. It adds to the body of observational evidence but does not replace prospective controlled studies.

When this study was published

Published in 2024, covering patients treated between 2015 and 2021. The findings are relevant to current clinical practice, particularly for liraglutide which remains widely prescribed for type 2 diabetes.

The bigger picture

The relationship between GLP-1 agonists and retinopathy remains a nuanced topic. Rapid HbA1c reduction can transiently worsen retinopathy regardless of the drug used, but GLP-1 drugs have faced particular scrutiny since the semaglutide SUSTAIN-6 signal. Real-world studies like this one from Saudi Arabia add geographic and ethnic diversity to the evidence base and consistently suggest that liraglutide does not independently worsen diabetic eye disease.

Questions still open

  • Does the reassuring retinopathy profile of liraglutide extend to more potent GLP-1 drugs like high-dose semaglutide?
  • Would patients with more severe retinopathy at baseline show different outcomes on liraglutide?
  • Are Middle Eastern populations at different baseline retinopathy risk that might affect the generalizability of these findings?

Common questions

Can GLP-1 drugs cause eye problems in diabetic patients?
This has been a concern since the semaglutide SUSTAIN-6 trial showed more retinopathy events. However, the issue may be related to rapid blood sugar lowering rather than the drug itself — any treatment that quickly reduces HbA1c can temporarily worsen retinopathy. This study of liraglutide found no worsening: most patients without eye disease stayed disease-free, and a quarter with existing retinopathy actually improved over 2 years.
What factors actually increase retinopathy risk in diabetic patients?
In this study, the factors significantly associated with retinopathy were: being on insulin (2.68x higher odds), having hypertension (2.56x), higher HbA1c levels, older age, and longer diabetes duration. These are all well-established retinopathy risk factors. Liraglutide use was not identified as an independent risk factor.

Read the original research

Retinopathy risk factors in patients with type 2 diabetes on liraglutide.

Medicine, 103(29), e39026

Citation

Mahzari, Moeber M; Alanazy, Abdulmalik M; Feroz, Zeeshan; Almani, Khalid M; Alghamdi, Meshari A; Almadani, Abdulaziz S; Alzahrani, Majed K; Alibrahim, Ahmed R; Badri, Motasim. (2024). Retinopathy risk factors in patients with type 2 diabetes on liraglutide.. Medicine, 103(29), e39026. https://doi.org/10.1097/MD.0000000000039026