Osilodrostat for Glycemic Control in Mild Autonomous Cortisol Secretion (MACS) With Difficult-To-Control Type 2 Diabetes - A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study

Trial details

Who runs it

Beckey Trinh

Trial code

NCT07922148

Record updated

6 November 2026

Original description

This single-centre, randomized, double-blind, placebo-controlled phase 2 trial investigates whether lowering cortisol with osilodrostat improves blood-glucose control in adults with mild autonomous cortisol secretion (MACS) and difficult-to-control type 2 diabetes. Forty-four participants are randomly assigned 1:1 to osilodrostat or matching placebo, taken once daily for 12 weeks, together with a blinded hydrocortisone/placebo for stress (sick-day) dosing. The primary outcome is the change in HbA1c from baseline to week 12; secondary outcomes include continuous glucose monitoring (CGM) metrics, cardiometabolic parameters, cortisol measures and quality of life. Participants are followed for a safety visit 4 weeks after the end of treatment.Read full original descriptionShow less

This single-centre, randomized, double-blind, placebo-controlled phase 2 trial investigates whether lowering cortisol with osilodrostat improves blood-glucose control in adults with mild autonomous cortisol secretion (MACS) and difficult-to-control type 2 diabetes. Forty-four participants are randomly assigned 1:1 to osilodrostat or matching placebo, taken once daily for 12 weeks, together with a blinded hydrocortisone/placebo for stress (sick-day) dosing. The primary outcome is the change in HbA1c from baseline to week 12; secondary outcomes include continuous glucose monitoring (CGM) metrics, cardiometabolic parameters, cortisol measures and quality of life. Participants are followed for a safety visit 4 weeks after the end of treatment.

Inclusion: Age 18 to <75 years; Confirmed MACS per ESE 2023 guidelines: serum cortisol >50 nmol/L after 1 mg dexamethasone suppression test, low ACTH and DHEAS, and uni-/bilateral adrenal adenoma(s) or macronodular/micronodular/diffuse bilateral adrenal hyperplasia on CT or MRI; Morning serum cortisol >300 nmol/L; Difficult-to-control type 2 diabetes: HbA1c >7.0% despite one of - ≥3 glucose-lowering medications; insulin plus ≥1 glucose-lowering medication; ≥2 glucose-lowering medications and ≥1 micro-/macrovascular complication; or ≥2 glucose-lowering and ≥2 blood-pressure-lowering medications; Stable background pharmacotherapy for ≥4 weeks before the first study visit; For persons of childbearing potential: agreement to abstinence or contraception with a failure rate ≤1%/year during treatment and for 1 month after the last dose.

Exclusion: Systemic glucocorticoid therapy within 3 months, or planned use; Current/recent intake of medications affecting adrenal steroidogenesis or cortisol assessment; Severe cardiovascular disease (NYHA class III-IV heart failure, myocardial infarction or unstable angina within the previous 6 months, or clinically significant arrhythmia); Known hypersensitivity to osilodrostat, its excipients, or the placebo; Malignant adrenal tumour; Type 1 diabetes; new-onset diabetes (<1 year); Severe psychiatric, medical or surgical illness; Uncontrolled arterial hypertension (≥ 160/100 mmHg despite therapy); Uncontrolled thyroid disease; History of breast or endometrial carcinoma; Concomitant therapy with clinically relevant drug-drug interactions with osilodrostat (strong CYP3A4 inhibitors; strong CYP3A4/CYP2B6 inducers; QT-prolonging medicinal products); Severe renal impairment (eGFR < 30 mL/min/1.73 m²), hemodialysis or end-stage renal disease; Refractory hypokalemia or hypomagnesemia (not correctable to K ≥4.0 and Mg ≥1.0 mmol/L before first dose); QTc > 480 ms on baseline ECG, or known congenital long QT syndrome; Age ≥75 years (osilodrostat not sufficiently studied in this age group per the SmPC); Planned adrenalectomy before completion of the study; Participation in another interventional trial within the last 30 days; Pregnancy or breastfeeding; WOCBP unwilling to use highly effective contraception; Excessive alcohol consumption; severe untreated sleep apnea; night-shift work; Liver cirrhosis Child-Pugh B or C.

ClinicalTrials.gov NCT07922148