Comparative ocular outcomes of tirzepatide versus other anti-obesity medications in people with obesity

Background: Obesity affects over one billion people worldwide and is associated with ocular complications, yet comparative effects of newer anti-obesity medications on eye health remain poorly understood. We examine ocular health outcomes among individuals with obesity receiving Tirzepatide, Semaglutide, Phentermine/Topiramate, Naltrexone/Bupropion, or Phentermine monotherapy. Methods: This propensity-score matched cohort study analyzed TriNetX US network data from November 2023 through April 2025. The study included matched pairs of obese individuals with a BMI ≥ 27 kg/m², comparing ocular outcomes between different anti-obesity medications. Primary outcomes included cataracts, oculomotor binocular dysfunction, visual disturbances, dry eye disease, ametropic accommodative dysfunction, and visual issues with blindness, assessed through Cox proportional hazards models with Bonferroni correction. Sensitivity analyses included BMI ≥ 30 kg/m² populations, subgroup stratification by clinical characteristics, and negative control outcomes to assess residual bias. Results: Here, we show that among 25,060 matched pairs comparing Tirzepatide with Semaglutide, no differences emerge across ocular outcomes. When compared with Naltrexone/Bupropion, Tirzepatide users show lower rates of cataracts (HR 0.46, 95% CI 0.23–0.92, p = 0.025) and oculomotor dysfunction (HR 0.31, 95% CI 0.16–0.60, p = 2.3 × 10−4). Semaglutide demonstrates similar patterns. Both medications show favorable profiles for visual disturbances, with Tirzepatide demonstrating lower rates versus Phentermine (HR 0.45, 95% CI 0.31–0.68, p = 7 × 10−5). Sensitivity analyses in the BMI ≥ 30 kg/m² population yield consistent results. Conclusions: Newer anti-obesity medications demonstrate differential associations with ocular outcomes compared to traditional agents. These findings may inform clinical decision-making regarding medication selection in obesity management, though prospective studies remain necessary to establish causal relationships.