CAPTAIN-T2D: Interim Results Display High Cortisol Prevalence in Difficult-to-Control T2D

Interim data from the phase 2 CAPTAIN-T2D trial have indicated a substantial unmet need among patients with difficult-to-control type 2 diabetes (T2D), specifically in elevated post-dexamethasone suppression test (DST) cortisol.1

Presented at the Endocrine Society (ENDO) Annual Meeting 2026 in Chicago, Illinois, by Elena Christofides, MD, the chief executive officer of Endocrinology Associates, scientific and medical advisor for Sparrow Pharmaceuticals, and a clinical associate professor at the Ohio University Heritage College of Osteopathic Medicine, this trial ultimately aims to evaluate clofutriben for the reduction of intracellular cortisol in several major tissues among these patients.1

In an interview with HCPLive, Christofides discussed the rationale for the trial’s structure, highlighting the unmet need faced by many patients with subtle cortisol increases. As most clinicians are trained to view hypercortisolism primarily – and sometimes exclusively – as an indication of classic Cushing’s syndrome, patients with less pronounced elevations are often missed or undertreated.

“We need to reframe the conversation around what the consequences are of elevated cortisol, and when we should intervene,” Christofides told HCPLive. “That’s the real struggle – we have been very dismissive as a general rule around the comorbidities associated with elevated cortisol, because it’s all too easy to blame societal changes, environmental changes, or personal changes, and so we end up gaslighting the patients about the disease process.”

Clofutriben is a selective inhibitor of human 11b-hydroxysteroid dehydrogenase type 1 (HSD-1), currently in development by Sparrow Pharmaceuticals to reduce intracellular cortisol in liver, adipose, muscle, and pancreas tissues, among others. Previous animal studies have indicated the drug’s efficacy in preventing corticosterone toxicities.1,2

The CAPTAIN-T2D trial aims to assess the prevalence of elevated cortisol in patients with difficult-to-control T2D, as well as attempting to establish clofutriben’s dose-response relationship for HbA1c reduction in these patients. Christofides and colleagues plan to investigate roughly 1500 patients – of these, 332 have been screened via DST to date.1

Difficult-to-control T2D was defined as HbA1c ≥7.5% despite ≥2 antidiabetic medications (ADMs), as well as the use of either ≥3 ADMs or ≥2 antihypertensives, or the presence of a diabetes complication, osteoporosis, or prior Cushing syndrome diagnosis. Following screening, investigators expect to enter roughly 210 patients with post-DST cortisol >1.8 µg/dL into 24 weeks of randomized, placebo-controlled treatment to identify the appropriate dose for HbA1c reduction in a future phase 3 trial.1

Of the 332 patients currently screened, 27.7% displayed post-DST cortisol levels >1.8 µg/dL. Analysis of demographic and clinical characteristics, including medications, T2D duration, and complications, as well as comorbidities and laboratory measures across post-DST cortisol categories is currently ongoing, according to Christofides and colleagues. In the meantime, the team has determined that, following their tracking of elevated post-DST cortisol in patients with difficult-to-control T2D, they have uncovered a significant unmet need in cardiometabolic disease. The full results of the study, including the response of HbA1c, body habitus, lipids, blood pressure, and other cardiometabolic risk factors to clofutriben, are expected to publish in Q4 2027.1

“The data is clear historically that patients who still have persistent hypercortisolism and disrupted rhythm, even if their comorbidities are managed, their mortality is increased,” Christofides said. “So, yes, look for a solution that may be surgical for that patient, because that’s obviously going to be curative for that person, but in the meantime, do not ignore the fact that they’re metabolically compromised and marching towards a premature death, while you ignore that metabolic abnormality looking for a surgical solution.”

Editors’ Note: Christofides reports disclosures with Ascendis, Eli Lilly, Novo Nordisk, Recordati, Corcept, Crinetics, and others.

References

1. Christofides E, Buse J, Fonseca V, et al. Prevalence of Elevated Cortisol in Difficult-to-Control Type 2 Diabetes: Interim Results for CAPTAIN-T2D, a Phase 2 Trial of Clofutriben. Abstract presented at the Endocrine Society (ENDO) Annual Meeting 2026, Chicago, IL. June 13-15, 2026.

2. Buttgereit F, Everding A, Andreica I, et al. Effects of clofutriben, a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, on the efficacy and toxicity of prednisolone in patients with polymyalgia rheumatica: a single-blind controlled trial with sequential cohorts. Ann Rheum Dis. 2026;85(5):921-931. doi:10.1016/j.ard.2025.10.015