Osilodrostat improves blood pressure and glycemic control in patients with Cushing's disease: a pooled analysis of LINC 3 and LINC 4 studies

Purpose: To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) and glycemic control in patients with Cushing’s disease. Methods: Pooled analysis of two Phase III osilodrostat studies (LINC 3 and LINC 4), both comprising a 48-week core phase and an optional open-label extension. Changes from baseline in systolic and diastolic BP (SBP and DBP), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were evaluated during osilodrostat treatment in patients with/without hypertension or diabetes at baseline. Results: Of 210 patients, 82.9% met criteria for hypertension and 40.0% for diabetes at baseline. In patients with hypertension, reductions in mean SBP/DBP were observed from week (W)12 to W72, and 49.1%/58.5% of patients with high SBP/DBP (> 130/>90 mmHg) at baseline had normotensive levels at W72. Antihypertensive medication dose was reduced/stopped in 26.8% of patients, and the proportion taking antihypertensive medication decreased from 54.3% at baseline to 47.3% at W72. In patients with diabetes, mean FPG and HbA1c decreased from W12 to W72, and 33.3%/61.5% with high FPG/HbA1c (≥ 100 mg/dL/≥6.5%) at baseline had normal levels at W72. Antihyperglycemic medication dose was reduced/stopped in 35.7% of patients, and the proportion taking antihyperglycemic medication decreased from 21.9% at baseline to 17.1% at W72; improvements in SBP/DBP and FPG/HbA1c were correlated with improvement in mean urinary free cortisol but not weight change. BP/glycemic parameters generally remained normal in patients without hypertension/diabetes at baseline. Conclusions: Patients with Cushing’s disease and comorbid hypertension/diabetes receiving osilodrostat had rapid and sustained improvements in SBP/DBP and glycemic control, respectively.