ObjectiveAssess incidence, severity, and outcomes of serum glucose excursions in patients with thyroid eye disease who received the insulin-like growth factor-1 receptor inhibitor, teprotumumab, during pivotal clinical trials. DesignAnalysis of pooled glycemic data and longitudinal trends. Subjectsphase 2 and phase 3 (OPTIC) pooled analysis: 170 patients (84 teprotumumab, 86 placebo); OPTIC-X: 51 patients from OPTIC. MethodsTeprotumumab administered as 8 intravenous infusions over 21 weeks. In the phase 2 trial, serum glucose was measured at weeks 1, 4, 15, and 21, with fasting blood collections weeks 1 and 4. In OPTIC and OPTIC-X, serum glucose was measured at each study visit, with fasting draws weeks 1 and 4 (non-diabetic patients) or all visits (diabetic patients). In all studies, hemoglobin A1c (HbA1c) was measured at baseline, 12, and 24 weeks plus weeks 36 and 48 of OPTIC-X. Main Outcome MeasuresSerum glucose and HbA1c over time. ResultsIn the pooled analysis, 9 hyperglycemic episodes were reported in 8 teprotumumab patients; mean HbA1c in teprotumumab patients increased 0.22% from baseline to week 24 (to 5.8%, range 5.0%–7.9%) versus 0.04% in placebo patients (to 5.6%, range 4.6%–8.1%). At study end, 78% of teprotumumab and 87% of placebo patients were normoglycemic. Normoglycemia was maintained from baseline to week 24 in 84% (57/68) of teprotumumab and 93% (64/69) of placebo patients. Of prediabetic patients, 43% (3/7) remained prediabetic in both groups and 29% (2/7) of teprotumumab and 14% (1/7) of placebo patients were diabetic at week 24. OPTIC-X showed a trend toward increased fasting glucose and HbA1c during teprotumumab retreatment and initial therapy (placebo patients from OPTIC). Fasting glucose commonly rose following the first 2-3 infusions and stabilized over subsequent infusions. Most hyperglycemic incidents occurred in patients with baseline prediabetes or diabetes and were controlled with medication. There was no evidence of progression or increased incidence of hyperglycemia with subsequent doses. ConclusionsSerious glycemic excursions are uncommon in patients who are normoglycemic before teprotumumab therapy. Patients with controlled diabetes or impaired glucose tolerance can be treated safely if baseline screening, regular monitoring of glycemic control, and treatment of hyperglycemia are ensured.