Teprotumumab-related hyperglycemia

Abstract Context Graves orbitopathy (GO) or thyroid eye disease is a potentially sight-threatening and disfiguring autoimmune disease. Teprotumumab is a monoclonal antibody against the insulin-like growth factor-I receptor that was recently approved for GO treatment. Hyperglycemia is a recognized adverse event of teprotumumab, occurring in 10% of patients in two recent randomized controlled trials. Objective Our study aimed to report the incidence, severity, management, and longitudinal glycemic changes in patients treated with teprotumumab in an academic practice cohort. Methods This longitudinal, observational study included all consecutive patients treated with teprotumumab between March 2020 and May 2022 at one institution. Hemoglobin A1c was measured every 3-months. Results Forty-two patients with baseline normoglycemia (n = 22), pre-diabetes (n = 10), and diabetes (n = 10) were followed for a mean of 47.5 weeks. Overall, HbA1c increased by 0.5% at 3-months. Least-square mean changes in HbA1c at 3 months were 1.3 (p < 0.001), 0.7 (p = 0.01), and 0.1 (p = 0.41) in patients with diabetes, pre-diabetes, and normoglycemia, respectively. Twenty-two patients (52%) had hyperglycemia which was graded as mild, moderate, and life-threatening in 55%(12/22), 41%(9/22), and 5%(1/22) of cases, respectively. Age, pre-existing diabetes, and Hispanic and Asian race/ethnicity were significant risk factors for hyperglycemia. Among patients with hyperglycemia, 36.4% (8/22) returned to baseline glycemic status at last follow-up. Conclusions While effective, teprotumumab carries a significant risk of hyperglycemia, especially in patients with diabetes. Hyperglycemia may persist after stopping teprotumumab. These findings underscore the importance of guidelines for screening and management of teprotumumab-related hyperglycemia.