CAPTAIN-T2D: New Trial Investigates Treating Elevated Cortisol in T2D, With Vivian Fonseca, MD

The phase 2 Clofutriben And Placebo Against INtractable Type 2 Diabetes (CAPTAIN-T2D) trial, investigating clofutriben to improve glycemic control and metabolic health in patients with difficult-to-control type 2 diabetes (T2D) and elevated cortisol, has officially enrolled its first patient.1

CAPTAIN-T2D directly follows positive results from the CATALYST trial in 2025, which saw 136 patients with T2D and hypercortisolism randomly assigned in a 2:1 ratio to either mifepristone 300-900 mg once daily (n = 91) or placebo (n = 45) for 24 weeks. The primary endpoint was the change in HbA1c, which worked out to a -1.32% difference compared to placebo. Additionally, patients receiving mifepristone saw reductions in body weight and waist circumference.2

“So, what we want to do now in CAPTAIN-T2D is to use another approach at treating this elevated cortisol,” Vivian Fonseca, MD, professor of medicine, assistant dean for clinical research, and the Tullis-Tulane Alumni Chair in Diabetes at Tulane University School of Medicine, told HCPLive in an exclusive interview. “In this instance, we’re using an 11-beta hydroxysteroid dehydrogenase inhibitor, which uses a completely different approach from mifepristone. You’re addressing intracellular cortisol by blocking this enzyme that leads to conversion of the inactive cortisone to cortisol, and so you’re decreasing cortisol activity in the tissues.”

CAPTAIN-T2D is a 2-part trial – the first part will see patients with poorly controlled T2D despite being on multiple medications screened for elevated cortisol using an overnight dexamethasone suppression test. This period will last between 5 and 9 weeks for most participants.3

Eligible patients will then be randomly assigned to either clofutriben 0.2 mg, 2 mg, 6 mg, or 12 mg, or a placebo control, all of which will be administered daily. This second part will last for 24 weeks, with a follow-up phone call 4 weeks after the final dose.3

To be eligible for inclusion, patients must be ≥18 years old with an HbA1c ≥7.5% documented within 3 months prior to screening. Additionally, patients require ≥1 of the following:

1. ≥3 stable and adequate ADMs
2. Diabetes complications – retinopathy, nephropathy, neuropathy, atherosclerotic cardiovascular disease
3. Hypertension needing ≥2 adequately dosed AHMs
4. Adequately dosed basal or basal plus prandial insulin on top of ≥1 other ADM
5. Adequately dosed incretin agonists on top of ≥1 other ADM
6. Evidence or history of osteoporosis or non-traumatic fracture
7. Established diagnosis of a neoplastic source of hypercortisolism and have failed, are ineligible for, or declined surgery.3

CAPTAIN-T2D has 2 primary endpoints: the first is the percentage of patients with both morning serum cortisol >1.8 mg/dL and morning plasma dexamethasone >-140 ng/dL after a single dexamethasone 1 mg dose taken the night prior. The second endpoint involves glycated hemoglobin A1c percent change from baseline to week 24 by treatment. Secondary endpoints include fasting plasma glucose change from baseline and the frequency of treatment-emergent adverse events.3

The trial is expected to enroll a total of 1500 patients and is planned to end in June of 2028.3

“We’ve begun to use this method a lot in other conditions, such as cancer: you find a particular defect, and you treat it with therapy that’s specifically targeted to that defect,” Fonseca said. “Unfortunately, we don’t have much of that in diabetes. We’ve been using a one-glove-fits-all approach, giving everybody every new medication that comes along, and the success has been mixed. Overall, control is better than it was 20 years ago, but it’s still not right, and I think identifying abnormalities could help with better outcomes.”

Editor’s Note: Fonseca reports disclosures with Abbott, AstraZeneca, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Bayer, and others.

References

1. Sparrow Pharmaceuticals. Sparrow Pharmaceuticals Announces First Patient Enrolled in Phase 2b Clinical Trial Evaluation Clofutriben for Difficult-to-Control Type 2 Diabetes. BioSpace. January 6, 2026. Accessed January 23, 2026. https://www.biospace.com/press-releases/sparrow-pharmaceuticals-announces-first-patient-enrolled-in-phase-2b-clinical-trial-evaluating-clofutriben-for-difficult-to-control-type-2-diabetes

2. DeFronzo RA, Fonseca V, Aroda VR, et al. Inadequately controlled type 2 diabetes and hypercortisolism: Improved glycemia with mifepristone treatment. Diabetes Care. 2025;48(12):2036-2044. doi:10.2337/dc25-1055

3. Sparrow Pharmaceuticals. Trial Against INtractable Type 2 Diabetes (CAPTAIN-T2D) (CAPTAIN-T2D). ClinicalTrials.gov Identifier: NCT07296484. Updated January 22, 2026. Accessed January 23, 2026. https://clinicaltrials.gov/study/NCT07296484?term=NCT07296484&rank=1