National Database Study Supports AMD Protective Effect in GLP-1 Drug Users

A new analysis published in Ophthalmology Retina using the TriNetX national cohort found that patients prescribed GLP-1 receptor agonists had a lower risk of developing either dry or wet AMD. However, it did not affect the rate of conversion to neovascular AMD among patients with the non-neovascular form at baseline. Photo: Tanuj P. Banker, MD. Click image to enlarge. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are currently some of the most in-demand and closely watched medications on the market. Primarily developed for treatment-resistant diabetes, these drugs have demonstrated benefits in multiple parts of the human body, including the cardiovascular and renal systems, and trials are underway exploring their impact on the nervous system. They’ve also exhibited protective effects against glaucoma and age-related macular degeneration (AMD). However, evidence on the latter is mixed, prompting a group of researchers from the Cleveland Clinic to strengthen the results of their own prior study using a national cohort. Their findings were just published in Ophthalmology Retina. According to their previous research, GLP-1 agonists were found to be protective against both dry and wet AMD when compared to patients taking insulin, but the authors mentioned an inability to fully propensity match for disease severity metrics such as body mass index (BMI) and hemoglobin A1c (HbA1c). This new study used the TriNetX US Collaborative Network platform, which contains data from nearly 120 million patients, and the researchers applied rigorous propensity matched cohorts of patients prescribed GLP-1 receptor agonists, alternate glucose-lowering meds or lipid-lowering drugs.  The results of this new study were as follows:Patients prescribed GLP-1 agonists had greater baseline chronic disease burden and worse disease severity metrics than comparator groups. Propensity matching effectively matched chronic disease prevalence at baseline. A GLP-1 drug prescription was associated with a significant reduction in hazard ratio (HR) for dry AMD compared to glucose-lowering medications over one (HR, 0.79), two (HR, 0.75) and three (HR, 0.77) years. Similar protective effects were observed when compared to lipid-lowering medications after two (HR 0.84) and three (HR 0.8) years.There was a significant reduction in risk of wet AMD with GLP-1 agonist prescription across all timepoints compared to both alternate glucose-lowering and lipid-lowering medications.There was no significant impact of GLP-1 drugs on risk of conversion from non-neovascular AMD at baseline to neovascular AMD.“Together, these results suggest that GLP-1RAs, albeit not clearly protective when it comes to neovascular AMD, do not promote conversion to neovascular AMD as has been recently reported,” the authors wrote in Ophthalmology Retina. One explanation for the reduced risk of wet AMD could be improved access to medical care in patients taking GLP-1 drugs, leading to earlier detection of dry AMD and reducing the likelihood of presenting with neovascular AMD as an initial diagnosis, they continued. “It is also possible that GLP-1RAs do not have a protective effect against neovascular conversion specifically but do have a general protective effect against developing non-neovascular AMD at baseline,” wrote the authors.  The authors noted some limitations of this new study, foremost their inability to reliably match patients by severity of baseline dry AMD. “It is known that patients with intermediate non-neovascular AMD demonstrate a higher risk of conversion compared to patients with early AMD, but this effect nor the impact of GLP-1RAs on this conversion rate was unable to be examined in this study due to limitations in numbers of patients and uncertainty of reliability in staging of earlier stages of non-neovascular AMD,” they wrote. Since TriNetX is not specific to eye care, researchers did not have access to other metrics such as visual acuity or geographic atrophy biomarkers, nor could they perform analyses on individual eyes, which precluded their ability to examine the effect on conversion of one eye if the fellow eye had already converted, they added. There are also possible limitations through ICD-10 coding and socioeconomic status, presenting an underrepresentation of patients with healthcare barriers.  Eyecare database–specific analyses or prospective trials should be conducted to further validate these results, the authors advocated. Given the substantial increase in patients being prescribed GLP-1 drugs in recent years, they wrote, it is critical to understand how this medication class influences ocular disease. Click here for the journal source. Allan KC, Cohn EF, Bala S, Kim SB, Kaelber DC, Singh RP, Talcott KE, Mammo DA, Rachitskaya AV. Glucagon-like peptide-1 receptor agonist use and risk of neovascular age-related macular degeneration in a national cohort study. Ophthalmology Retina. November 3, 2025. [Epub ahead of print.]This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.