A recent study published in Ophthalmology investigated whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) impact the risk for age-related ocular diseases.
Give me some background.
Inflammation and oxidative stress are key drivers of aging and contribute to age-related ocular diseases like age-related macular degeneration (AMD), cataracts, and glaucoma.
While there are clinical trials in progress for novel drug discovery to address these factors, an alternative and efficient method to bring drugs to clinic is through drug repurposing.
Bring in GLP-1 RAs.
GLP-1 RA use has drastically increased over the past 5 years—and while historically used for managing type 2 diabetes, its indications have expanded to obesity and prevention of cardiovascular death in obese or overweight patients.
- In addition: Researchers are interested in understanding its anti-inflammatory, antioxidant, and anti-apoptotic effects in cardiovascular, respiratory, hepatic, and neurologic organs.
As such: A research team from the Case Western Reserve University School of Medicine sought to elucidate the potential protective effects of GLP-1 RAs against age-related ocular diseases.
Now talk about the study.
In this retrospective cohort study, investigators used the TriNetX database to identify relevant electronic health records (EHRs) of patients in the United States.
They included patients 60+ years old with at least 5 years of ophthalmology follow-up and medication prescription documentation.
These patients were then organized into five medication groups:
- GLP-1 RAs
- Metformin
- Insulin
- Statins
- Aspirin
The cohorts were propensity-matched on demographic characteristics and chronic health conditions.
Main outcome measures?
After 5 years from the initial medication prescription, outcomes of the following diseases were compared:
- Cataract
- Ocular hypertension (OHT)
- Primary open-angle glaucoma (POAG)
- Non-exudative age-related macular degeneration (AMD)
- Exudative AMD
Findings?
Of the 9,669 patients taking GLP-1 RAs, 84.4% were diabetic, with an average body mass index (BMI) of 36.2 kg/m2.
Propensity-matched cohorts showed that GLP-1 RAs were associated with a reduced hazard of non-exudative AMD compared to:
- Metformin (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.56-0.84)
- Insulin (HR 0.72, 95% CI 0.58-0.89)
- Statins (HR 0.70, 95% CI 0.57-0.87)
These findings were validated by comparing them to aspirin and in an independent older cohort of patients.
Tell me more.
A significant reduction in the risk of non-exudative AMD occurred after 3 years compared to:
- Metformin (HR 0.69, 95% CI 0.52-0.91)
- Insulin (HR 0.66, 95% CI 0.50-0.87)
- Statins (HR 0.67, 95% CI 0.51-0.88)
Time course results were validated using independent cohorts of propensity-matched patients taking medications for 3 years.
Anything else?
Of note, GLP-1 RAs also significantly reduced the risk of exudative AMD (HR 0.70, 95% CI 0.58-0.84) and POAG (HR 0.58, 95% CI 0.45-0.76) compared to insulin after 3 years.
Usage of GLP-1 RAs demonstrated no persistent, significant impact on the risk of cataract formation or OHT after 5 years compared to other medications.
Limitations?
These included:
- Reliance on International Classifications of Diseases (ICD) / Current Procedural Terminology (CPT) code accuracy in the TriNetX database
- The TriNetX platform is not ophthalmology specific, meaning they could not analyze metrics such as visual acuity or ophthalmic imaging
- The retrospective study design
- This study did not analyze socioeconomic factors that could influence ocular disease severity between groups
- Errors or variations in coding practices could underestimate or misrepresent chronic health factors used during propensity matching, such as smoking status
- The investigators could not control for the use of Age-Related Eye Disease Study (AREDS) vitamins, follow-up frequency, or drug dosage, which could confound results
Take home.
These findings suggest that GLP-1 RAs may reduce the risk of non-exudative AMD and potentially promote a protective effect against glaucoma.
Therefore: These results indicate the need for future prospective studies to validate these findings.
Next steps?
Future studies could use ophthalmology-specific databases or multi-center retrospective chart reviews to better characterize the impact of GLP-1 RA on the different stages of AMD pathogenesis.
Further: Additional studies should examine the dose-dependent effects of GLP-1 RAs, especially given the potential to differentiate between patients receiving medication at the higher dosage for weight loss compared to lower doses for diabetes management, the study authors noted.