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Diabetes and Vascular Disease

SAT-634 - Prevalence of Elevated Cortisol in Difficult-to-Control Type 2 Diabetes: Interim Results for CAPTAIN-T2D, a Phase 2 Trial of Clofutriben

Saturday, June 13, 2026
9:30 AM - 4:30 PM CT
Background
Cortisol regulates carbohydrates, lipids, and blood pressure (BP), which are all critical to cardiometabolic disease. Difficult-to-control (DTC) type 2 diabetes (T2D) and resistant hypertension (rHTN) are disproportionately associated with elevated cortisol (EC) of neoplastic (i.e., Cushing syndrome [CS], autonomous cortisol secretion [ACS]) and non-neoplastic origin. The association is stronger in patients with T2D and HTN complications, resistance to highly effective antidiabetic medications (ADMs; e.g., incretin analogs), and cardiometabolic comorbidities, suggesting a potential role for a safe, cortisol-targeted therapy in managing cardiometabolic disease.
Clofutriben (CLO), an oral 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, reduces intracellular cortisol in important tissues (e.g., liver, adipose, muscle, pancreas) by inhibiting its regeneration from cortisone. It has been shown to reduce HbA1c and improve other cardiometabolic parameters in patients with T2D and either CS or painful diabetic neuropathy. The CAPTAIN-T2D trial will 1) assess the prevalence of EC in DTC T2D, and 2) establish CLO’s dose-response relationship for HbA1c reduction.
Methods
Approximately 1500 participants in this response-adaptive-randomized, placebo-controlled, dose-range finding trial with DTC T2D (HbA1c ≥7.5% despite ≥2 ADMs and either use of ≥3 ADMs or ≥2 antihypertensives or presence of a diabetes complication, osteoporosis, or prior CS diagnosis ) will be assessed by overnight dexamethasone suppression test (DST) at approximately 50 US sites. After screening for, and exclusion of, correctable CS, approximately 210 eligible participants with valid post-DST cortisol >1.8 µg/dL enter 24 weeks of randomized, placebo-controlled treatment with intent to identify the dose(s) most appropriate for HbA1c reduction in Phase 3. Participants with repeat DST cortisol >5.0 µg/dL may participate in the interventional part only after consultation on medical and surgical options for neoplastic disease.
Results
Among the 332 participants screened by DST to date, 27.7% exhibited post-DST cortisol levels >1.8 µg/dL. Analysis of demographic and clinical characteristics (e.g., medications, T2D duration and complications), comorbidities, and laboratory measures across post-DST cortisol categories (≤1.2, >1.2–≤1.8, >1.8–≤5.0, and >5.0 µg/dL) is ongoing.
Conclusion
Elevated post-DST cortisol from a dysregulated HPA axis in DTC T2D and rHTN have been tracked in recent trials of similar design. Replication of these results in DTC T2D confirms the high unmet need in cardiometabolic disease. The specific etiology of these elevations and the full results of the blinded intervention, including response of HbA1c, body habitus, BP, lipids, and other cardiometabolic risk factors to CLO must await the trial’s completion (expected Q4 2027).

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