Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Cataract Development.

OBJECTIVE: To evaluate the risk of developing age-related cataract among nondiabetic patients who are overweight or obese prescribed glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared to other weight loss drugs (OWLD). DESIGN: Retrospective cohort study using the TriNetX Global Collaborative Network. SUBJECTS: Overweight or obese patients aged 55 years and greater were included. Patients with a diabetes mellitus or prior age-related cataract were excluded. METHODS: Patients in the GLP-1RA group were prescribed either semaglutide or liraglutide. Patients in the OWLD group were lorcaserin, setmelanotide, diethylpropion, sibutramine, fenfluramine, mazindol, phentermine, or orlistat A third cohort included patients not prescribed any weight loss medications. Propensity score matching was performed to minimize baseline differences between cohorts. MAIN OUTCOME MEASURES: The primary outcome was development of age-related cataract at 5-, 7-, and 10-year intervals. Risk ratios with 95% confidence intervals and corresponding P-values were reported. Standardized mean differences (SMDs) were calculated to assess covariate balance. RESULTS: In the primary analysis of GLP-1RA vs OWLD usage, covariate balance was achieved across all matched variables with SMDs < 0.2. In this primary analysis, GLP-1RA use was associated with a decreased risk of age-related cataract at 5 (RR: 0.278; 95% CI: 0.246-0.314; P < .0001), 7 (RR: 0.269; 95% CI: 0.241-0.299; P < .0001), and 10 (RR: 0.198; 95% CI: 0.176-0.222; P < .0001) years compared to OWLD use. GLP-1RA use was also associated with decreased risk at 5 (RR: 0.605; 95% CI: 0.553-0.661; P < .0001), 7 (RR: 0.499; 95% CI: 0.458-0.542; P < .0001), and 10 (RR: 0.437; 95% CI: 0.403-0.475; P < .0001) years compared to no drug use. Conversely, OWLD use was associated with increased risk at 5 (RR: 2.142; 95% CI: 1.957-2.345; P < .0001), 7 (RR: 2.093; 95% CI: 1.931-2.268; P < .0001) and 10 (RR: 2.111; 95% CI: 1.961-2.273; P < .0001) years compared to no drug use. CONCLUSIONS: GLP-1RA use was associated with a significantly reduced risk of age-related cataract compared to OWLD use and no pharmacologic treatment. These findings support the need for randomized prospective trials and mechanistic studies to better understand this observed association.