Evaluating the Ocular Safety Profile of Glucagon-Like Peptide-1 Receptor Agonists
Poster #: 092
Session/Time: A
Author:
Zaid Shuja Khan, MS
Mentor:
Rohit Adyanthaya, MD
Research Type: Clinical Research
Abstract
INTRODUCTION:
The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has surged, yet their ocular safety profile remains inconclusive. Initial concerns were raised by the SUSTAIN-6 trial, which found that users of semaglutide had a significantly increased risk of developing retinal complications (HR, 1.76; 95% CI, 1.11-2.78; P= 0.02). However, the understanding of GLP-1RAs' association with diabetic retinopathy (DR), along with other ocular pathologies such as neovascular age-related macular degeneration (nAMD) and glaucoma remains inconclusive. We aimed to clarify the association between GLP-1RA use and ocular risk.
METHODS:
We conducted three parallel, retrospective, new-user, propensity-score-matched (PSM) cohort studies using the TriNetX Global Federated Health Research Network. New users of GLP-1RAs with type 2 diabetes were matched 1:1 to new users of SGLT-2 inhibitors (for nAMD and DR analyses) or DPP-4 inhibitors (for the glaucoma analysis). The models controlled for demographics, comorbidities, labs, and healthcare utilization proxies. Primary outcomes were based on diagnostic codes indicating disease progression, with confirmatory sensitivity analyses using procedure codes. Hazard Ratios (HRs) were calculated using Cox proportional hazards models.
RESULTS:
Matched cohorts included 1,026 pairs (nAMD), 215,429 pairs (glaucoma), and 8,412 pairs (DR). For nAMD and DR, there was no significant difference in the risk of diagnosis of progressed disease or requiring a procedure related to disease progression (all P >0.05). Glaucoma analysis revealed a significant, 34% lower risk of requiring a glaucoma-related procedure for GLP-1RA users (HR, 0.66; 95% CI, 0.55-0.80; P< 0.001), while showing no significant difference in the risk of a glaucoma diagnosis (P= 0.26).
CONCLUSION:
The analysis supports the relative safety of GLP-1RA use and may suggest a potential slowing effect against glaucoma progression relative to active comparators that warrants further investigation.
The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has surged, yet their ocular safety profile remains inconclusive. Initial concerns were raised by the SUSTAIN-6 trial, which found that users of semaglutide had a significantly increased risk of developing retinal complications (HR, 1.76; 95% CI, 1.11-2.78; P= 0.02). However, the understanding of GLP-1RAs' association with diabetic retinopathy (DR), along with other ocular pathologies such as neovascular age-related macular degeneration (nAMD) and glaucoma remains inconclusive. We aimed to clarify the association between GLP-1RA use and ocular risk.
METHODS:
We conducted three parallel, retrospective, new-user, propensity-score-matched (PSM) cohort studies using the TriNetX Global Federated Health Research Network. New users of GLP-1RAs with type 2 diabetes were matched 1:1 to new users of SGLT-2 inhibitors (for nAMD and DR analyses) or DPP-4 inhibitors (for the glaucoma analysis). The models controlled for demographics, comorbidities, labs, and healthcare utilization proxies. Primary outcomes were based on diagnostic codes indicating disease progression, with confirmatory sensitivity analyses using procedure codes. Hazard Ratios (HRs) were calculated using Cox proportional hazards models.
RESULTS:
Matched cohorts included 1,026 pairs (nAMD), 215,429 pairs (glaucoma), and 8,412 pairs (DR). For nAMD and DR, there was no significant difference in the risk of diagnosis of progressed disease or requiring a procedure related to disease progression (all P >0.05). Glaucoma analysis revealed a significant, 34% lower risk of requiring a glaucoma-related procedure for GLP-1RA users (HR, 0.66; 95% CI, 0.55-0.80; P< 0.001), while showing no significant difference in the risk of a glaucoma diagnosis (P= 0.26).
CONCLUSION:
The analysis supports the relative safety of GLP-1RA use and may suggest a potential slowing effect against glaucoma progression relative to active comparators that warrants further investigation.