Teprotumumab-Associated Hyperglycemia: A Large-Scale Multinational Cohort Study

OBJECTIVE: Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, represents the first Food and Drug Administration (FDA)-approved treatment for thyroid eye disease (TED). However, hyperglycemia has emerged as a significant adverse event, with limited real-world data on its incidence and clinical impact. This study aimed to evaluate the risk of glycemic abnormalities associated with teprotumumab treatment using a large, multinational electronic health records database. METHODS: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, which includes data from more than 165 health care organizations worldwide. Patients with TED treated with teprotumumab were matched 11 to TED patients who did not receive teprotumumab using propensity score matching (PSM). The primary outcomes were incident prediabetes, diabetes, hyperglycemia defined by a random blood glucose level ≥200 mg/dL, and initiation of antidiabetes medications during follow-up ranging from 6 months to 5 years. Time-to-event analyses were performed using Kaplan-Meier survival curves to estimate cumulative incidence over time. RESULTS: After PSM, 792 teprotumumab-treated patients were compared with 792 matched controls over a follow-up period of up to 5 years. Teprotumumab treatment was associated with a significantly increased risk of prediabetes at 5 years (HR: 2.03, CI: 1.51-2.72), affecting 24% of treated patients compared with 10% of controls. The risk of incident diabetes at 5 years was also significantly higher in the teprotumumab-treated patients (HR: 2.23, CI: 1.46-3.43). Teprotumumab-treated patients were more likely to require the addition of antidiabetes medications at 5 years (HR: 1.68, CI: 1.27-2.22). CONCLUSIONS: In this large-scale cohort study, teprotumumab treatment was associated with an increased risk of dysglycemia. Although this risk was observed across several glycemic outcomes, the absolute risk increase was modest. These findings support routine glucose monitoring and proactive glycemic management, while emphasizing the importance of individualized risk-benefit assessment when considering teprotumumab therapy in patients with TED.