Vivian Fonseca, MD, is professor of medicine, assistant dean for clinical research, and the Tullis-Tulane Alumni Chair in Diabetes at Tulane University School of Medicine.

Vivian Fonseca, MD

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 

 and elevated cortisol, has officially enrolled its first patient.

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.

“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 

 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.

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.

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:

Diabetes complications – retinopathy, nephropathy, neuropathy, 

Hypertension needing ≥2 adequately dosed AHMs

Adequately dosed basal or basal plus prandial insulin on top of ≥1 other ADM

Adequately dosed incretin agonists on top of ≥1 other ADM

Evidence or history of osteoporosis or non-traumatic fracture

Established diagnosis of a neoplastic source of hypercortisolism and have failed, are ineligible for, or declined surgery.

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.

The trial is expected to enroll a total of 1500 patients and is planned to end in June of 2028.

“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.

Sparrow Pharmaceuticals. Sparrow Pharmaceuticals Announces First Patient Enrolled in Phase 2b Clinical Trial Evaluation Clofutriben for Difficult-to-Control Type 2 Diabetes. 

. 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

DeFronzo RA, Fonseca V, Aroda VR, et al. Inadequately controlled type 2 diabetes and hypercortisolism: Improved glycemia with mifepristone treatment. 

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

Videos

Fonseca explains the structure and goals of the ongoing trial, which has enrolled its first patient to clofutriben treatment against hard-to-control T2D.

Panelists discuss how improving adherence requires both individual strategies like smartphone reminders and smart medication monitoring devices, as well as population-level interventions including reducing sodium content in processed foods and harmonizing hypertension guidelines to address the epidemic of poorly controlled blood pressure.

Optimizing Patient Adherence and Targeting the Root Causes of Treatment Resistance 

Video content above is prompted by the following: 

Modern adherence improvement strategies leverage smartphone technology and digital health tools to address the fundamental challenge of medication-taking persistence. Smart medication caps, phone alarms, and remote monitoring systems provide objective data about patient medication-taking behavior while enabling more targeted interventions. These technological solutions must be implemented thoughtfully, recognizing that opening a pill bottle doesn’t guarantee medication consumption, but they provide valuable conversation starters between patients and providers.

Addressing resistant hypertension requires population health approaches targeting root causes, particularly dietary sodium reduction through food industry regulation. International examples from the UK demonstrate that reducing sodium content in processed foods can achieve meaningful population-level blood pressure improvements. Public health initiatives must balance individual choice with protective policies, similar to approaches used for clean water and food safety, recognizing that personal responsibility alone cannot address the epidemic of poor blood pressure control.

The future of hypertension management lies in addressing underlying causes rather than simply adding medications indefinitely. This includes governmental leadership in food policy, health care system redesign for chronic disease management, and individual education about lifestyle modifications. The goal is creating environments where patients who want to maintain good health can do so without being undermined by unhealthy food systems, while preserving individual choice and autonomy in health care decisions.

Panelists discuss how newer therapies will likely be incorporated into guidelines with improved reimbursement structures over time, similar to the evolution seen with lipid-lowering medications, making advanced treatments more accessible for patients with uncontrolled blood pressure.

Integration of Newer Agents Into Future Guidelines

Future hypertension guidelines will likely incorporate newer therapeutic options like endothelin receptor antagonists and renal denervation more prominently as evidence accumulates. The field is moving toward more precision-based approaches, attempting to match specific patient phenotypes with optimal therapeutic interventions rather than universal treatment algorithms. This evolution requires better characterization of patient subgroups and their differential responses to various antihypertensive mechanisms.

Health care reimbursement structures will need to evolve to support newer, more expensive antihypertensive therapies, similar to the progression seen with lipid-lowering medications beyond statins. Current barriers to accessing advanced therapies like endothelin receptor antagonists or renal denervation procedures will likely diminish as guidelines incorporate these options and demonstrate their cost-effectiveness. Payers will increasingly recognize that leaving patients on inadequate generic therapy with blood pressures in the 130-140 mm Hg range is not appropriate long-term management.

The integration of newer agents into clinical practice faces challenges beyond regulatory approval and guideline inclusion. Clinicians need education about appropriate patient selection, timing of advanced therapies, and combination strategies. The field must address both the development of novel therapeutic options and the health care delivery systems needed to implement them effectively, ensuring that innovation translates into improved population-level blood pressure control rates.

Panelists discuss how follow-up strategies should include monthly visits initially with more frequent monitoring for high-risk situations, emphasizing home blood pressure monitoring and utilizing team-based care approaches with optimal visit intervals of 4 to 6 weeks to avoid both therapeutic inertia and overadjustment.

Lab Monitoring or Follow-Up Strategies With New Agents

Resistant hypertension management requires strategic follow-up scheduling with most patients seen within 4 to 6 weeks after medication changes. The A-TIME study demonstrated that 2-week intervals are too frequent, leading to excessive changes and reduced adherence, while 3-month intervals are inadequate for optimal control. High-risk patients, particularly those with elevated potassium levels or kidney disease, may require laboratory monitoring within 1 to 2 weeks when starting medications affecting electrolyte balance.

Home blood pressure monitoring represents a cornerstone of resistant hypertension management, providing more accurate assessment than office readings affected by white coat effects. Proper cuff sizing and patient education are essential for reliable home monitoring data. Remote patient monitoring technologies and team-based care approaches, including clinical pharmacists and physician extenders, help overcome access barriers and therapeutic inertia that commonly plague resistant hypertension management.

Successful resistant hypertension management requires systematic approaches to prevent patient loss to follow-up, which contributes significantly to treatment resistance. Health care teams must implement systems to identify and reengage patients who miss appointments, as prescription persistence requires multiple successful interactions over years. Virtual care options have expanded access for patients with transportation or mobility barriers, though individual patient preferences for in-person versus virtual visits should guide delivery methods.

Vivian Fonseca, MD

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