Plain Language Summary
Retrospective cohort study using TriNetX US Collaborative Network comparing diabetic retinopathy diagnosis, progression, and ocular intervention rates between tirzepatide users and matched lifestyle-intervention-only controls in diabetes with overweight/obesity. Evaluates whether tirzepatide reduces long-term DR risk. Provides the first large-scale US observational evidence for tirzepatide's long-term retinal effects in diabetes—testing whether the metabolic improvements from dual GIP/GLP-1 agonism translate to reduced DR incidence and progression despite the theoretical early worsening concern from rapid HbA1c reduction.
Abstract
PURPOSE: Tirzepatide, recently Food and Drug Administration (FDA) approved for weight loss, offers substantial metabolic benefits, yet its long-term impact on diabetic retinopathy (DR) remains unclear. The study purpose was to compare the risk of DR diagnoses, progression, and need for ocular interventions between patients using tirzepatide and matched patients receiving lifestyle intervention alone.
DESIGN: Population-based, retrospective cohort study using the TriNetX US Collaborative Network.
PARTICIPANTS: Patients with diabetes and overweight or obesity who initiated tirzepatide were included. Each tirzepatide patient was propensity score matched to a similar patient who received lifestyle intervention alone and had no exposure to weight-loss drugs.
METHODS: Initiation of tirzepatide.
MAIN OUTCOME MEASURES: Onset of DR, progression to more severe stages of DR, or need for interventions, such as intravitreal anti-VEGF injection and pan-retinal photocoagulation.
RESULTS: After propensity matching for demographic, metabolic, and systemic covariates, 173 846 patients were included in the analysis (86 923 per cohort; mean [standard deviation] age, 56.9 [12.7] years; 86 740 [52.0%] women). Tirzepatide use was associated with reduced 12-month risk of DR incidence and worsening events than the lifestyle intervention alone cohort, including incident mild nonproliferative diabetic retinopathy (NPDR) (risk ratio [RR], 0.864 [95% confidence interval {CI}, 0.758-0.985], proliferative diabetic retinopathy (PDR) (RR, 0.705 [0.564-0.882]), DR with macular edema (RR, 0.624 [0.536-0.727], vitreous hemorrhage (RR, 0.607 [0.429-0.860]), tractional retinal detachment (RR, 0.370 [0.179-0.765], intravitreal anti-VEGF injection (RR, 0.479 [0.368-0.625]), and pan-retinal photocoagulation (RR, 0.610 [0.403-0.924]).
CONCLUSIONS: Tirzepatide was associated with a lower incidence of new or progressive DR and fewer complications, including those requiring interventions, compared with lifestyle intervention alone. These findings may inform treatment selection for patients at risk for DR.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Authors
Shah, Jaffer; Razavi, Peyman; Festok, Muhamad; Ahmed, Harris; Mahrous, M Abdallah; Kovacs, Kyle D; Kiss, Szilárd