Glucagon-Like Peptide-1 Receptor Agonists and Ocular Outcomes: Metabolic Transition, Retinal Vulnerability, and Risk-Stratified Monitoring

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin-based therapies provide marked reductions in glycosylated hemoglobin (HbA1c), body weight, and cardiovascular risk. As global adoption expands and recognition of their broad metabolic benefits grows, clinical attention is shifting toward potential secondary complications, including ocular manifestations, during rapid metabolic improvement. This narrative review synthesizes evidence from randomized trials, meta-analyses, and observational studies up to 2026 to evaluate the effects of GLP-1-based therapies on various ocular outcomes. Recent meta-analyses demonstrate an overall neutral long-term risk for diabetic retinopathy (DR) and macular edema. Transient early worsening of DR occurs primarily in patients with advanced baseline disease and rapid HbA1c reductions, reflecting a metabolic transition phenomenon rather than intrinsic retinal toxicity. This interpretation is supported by 2024 cardiovascular outcome data in a non-diabetic population (e.g., Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT] trial) that showed no increased ocular risk. Observational data suggest protective associations with glaucoma via intraocular pressure-independent neuroprotection and a reduced risk of incident age-related macular degeneration, but a potential safety signal for nonarteritic anterior ischemic optic neuropathy has emerged in recent datasets. Although the absolute incidence remains low, risk with a delayed temporal pattern appears to be increased in specific cohorts. Emerging evidence also suggests potential benefits in ocular surface homeostasis and uveitis. Accordingly, following a 2025 multidisciplinary expert consensus, risk-stratified ophthalmic monitoring, rather than routine treatment avoidance, is recommended during the early metabolic transition in high-risk diabetic patients.