BOSTON, Nov. 05, 2026 (GLOBE NEWSWIRE) — Sparrow Pharmaceuticals, Inc., a targeted cardiometabolic therapeutics company, today announced the addition of expansion cohorts to the ongoing Phase 2b CAPTAIN-T2D trial (NCT07296484) of clofutriben, a novel, once-daily, oral HSD-1 inhibitor, in patients with difficult-to-control (DTC) type 2 diabetes (T2D). HSD-1 inhibition lowers intracellular cortisol, a biological target that today’s standards of care do not address. The original, dose-ranging cohorts of CAPTAIN-T2D are enrolling up to approximately 210 patients with post-dexamethasone suppression test (DST) cortisol greater than 1.8 µg/dL. The expansion cohorts will enroll approximately 80 additional patients with post-DST cortisol at or below 1.8 µg/dL to evaluate whether clofutriben’s efficacy benefits and safety extend across the entire range of cortisol levels in inadequately controlled T2D.

Cortisol is an underrecognized driver of treatment resistance and comorbidities in cardiometabolic disease. Interim data from CAPTAIN-T2D, presented at ENDO 2026, showed that among 397 DTC T2D patients screened, 77.1% had post-DST cortisol ≥0.9 µg/dL, a level that has been reported to be associated with an increased prevalence of cardiovascular disease. Multiple studies have identified post-DST cortisol lower than 1.8 µg/dL as being associated with increased cardiometabolic morbidity and adverse outcomes1,2,3,4,5. A cortisol-directed agent benefited patients with treatment-resistant T2D and post-DST cortisol greater than 1.8 µg/dL6. However, this is the first time that a cortisol-directed agent has been tested in DTC T2D in patients with lower post-DST cortisol.

“The 1.8 µg/dL threshold was not developed to predict response to cortisol-directed antihyperglycemic therapy,” commented Frank Czerwiec, M.D., Ph.D., Chief Medical Officer of Sparrow Pharmaceuticals. “Cortisol is critical to glucose regulation in everyone with T2D. By evaluating clofutriben in patients across the entire range of post-DST cortisol levels, CAPTAIN-T2D may help us to identify a better threshold, or to understand if clofutriben can have meaningful benefits across the entire population of inadequately controlled T2D.”

About CAPTAIN-T2D
CAPTAIN-T2D is a randomized, double-blind, placebo-controlled, dose-ranging Phase 2b trial being conducted in the United States. Part 1 (Screening) is expected to evaluate up to approximately 1,500 patients with T2D and EC risk factors. In Part 2 (Treatment), up to approximately 210 patients in the dose-ranging cohorts will be randomized to placebo or one of four once-daily oral doses of clofutriben [0.6, 2, 6, or 12 mg], for a 24-week treatment period. The expansion cohorts will be randomized independently of the main cohort, 4:1, to clofutriben 12 mg once daily or placebo.

The primary endpoint is change from baseline in hemoglobin A1c (HbA1c) at Week 24, which will be used to characterize the dose-response relationship and identify one or more doses for Phase 3. The degree of HbA1c response and overall safety will also support selection of an appropriate patient population for Phase 3. Exploratory endpoints will assess changes in other cardiometabolic measures that can be impacted by cortisol including body weight, blood pressure, cholesterol, and bone formation markers. Learn more at ClinicalTrials.gov (NCT07296484).

About Sparrow Pharmaceuticals
Sparrow Pharmaceuticals is a targeted cardiometabolic therapeutics company delivering breakthrough solutions for the millions of patients who struggle to control diabetes, obesity, hypertension, and related conditions with current therapies. The Company’s lead candidate, clofutriben, is a novel, once-daily, oral HSD-1 inhibitor currently in Phase 2b development for inadequately controlled type 2 diabetes, a large population with high unmet needs. HSD-1 inhibition is a novel mechanism that complements existing agents by modulating cortisol, an underlying driver of disease progression and treatment resistance across a spectrum of metabolic dysfunction. Clofutriben has been associated with improved glycemic control and other metabolic improvements while generally safe and well tolerated in multiple clinical trials without requiring dose titration. To learn more, visit https://sparrowpharma.com/ or follow us on LinkedIn.

Media Contacts
Maggie Whitney
LifeSci Communications
mwhitney@lifescicomms.com

References:

  1. Trandafir, AI and Caroste, M. Dexamethasone Suppression Testing in Patients with Adrenal Incidentalomas with/without Mild Autonomous Cortisol Secretion: Spectrum of Cortisol Cutoffs and Additional Assays (An Updated Analysis) Biomedicines. 2025. 13(9), 2169; https://doi.org/10.3390/biomedicines13092169
  2. Pelsma, ICM; Fassnacht, M; Tsagarakis, S; Terzolo, M; Tabarin , A; Sahdev, A; Newell-Price, J; Marina, L; Lorenz, K; Bancos, I; Arly, W; Dekkers, OM. Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis. European Journal of Endocrinology. 2023. DOI: 10.1093/ejendo/lvad134
  3. Prete, A and Bancos, I. Mild Autonomous cortisol secretion: pathophysiology, comorbidities and management approaches. Nature Reviews Endocrinology. 2024 Aug;20(8):460-473. doi: 10.1038/s41574-024-00984-y.Epub 2024 Apr 22.
  4. Kokoszka, J; Opalinska, M; Kolasa, M; Sitarz, K; Banas, A; Pabian, G; Bugajska, J; Sztefko, K; Hubalewska-Dydejczyk, A. Does the cutoff point of 1.8 ug/dl in the 1mg dexamethasone suppression test differentiate the cardiometabolic risk attributed to MACS? Endocrine Abstracts (2025) 110 P134 | DOI: 10.1530/endoabs.110.P134
  5. Auchus, R. HCP Live. Hypercortisolism in Patients with Treatment-Resistant Type 2 Diabetes, with Richard Auchus, MD, PhD. 2025. https://www.hcplive.com/view/hypercortisolism-in-patients-with-treatment-resistant-type-2-diabetes-with-richard-auchus-md-phd
  6. DeFronzo, R. et al. Inadequately Controlled Type 2 Diabetes and Hypercortisolism: Improved Glycemia With Mifepristone Treatment. Diabetes Care 2025;00(00):1–9 | https://doi.org/10.2337/dc25-1055


Primary Logo

Media gallery

About The Author
Sparrow Pharmaceuticals