Korlym® improved HbA1c, weight, and waist circumference in hypercortisolism patients with difficult-to-control type 2 diabetes, including those on GLP-1 therapies, according to ADA 2026 CATALYST trial data. MOMENTUM findings highlight widespread underdiagnosis of hypercortisolism in resistant hypertension.
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
New data presented at the American Diabetes Association (ADA) 86th Scientific Sessions reinforce the role of endogenous hypercortisolism in treatment-resistant cardiometabolic disease. Corcept Therapeutics reported updated findings from its Phase 4 CATALYST study (NCT05772169) showing that Korlym® (mifepristone) improved glycemic control and metabolic parameters in patients with hypercortisolism and difficult-to-control type 2 diabetes, including those already receiving GLP-1-based therapies.
Cortisol Excess and Metabolic Dysfunction
Hypercortisolism, commonly known as Cushing’s syndrome, results from excessive cortisol activity and is associated with obesity, hypertension, insulin resistance, hyperglycemia, and cardiovascular complications. Cortisol excess can impair incretin signaling, reduce pancreatic beta-cell function, and worsen insulin resistance, limiting the effectiveness of standard diabetes therapies.
Korlym, a cortisol receptor antagonist, blocks cortisol’s effects rather than reducing its production. It is FDA-approved to control hyperglycemia secondary to endogenous Cushing’s syndrome in adults with type 2 diabetes or glucose intolerance who are not surgical candidates or who have not responded adequately to surgery.
CATALYST Demonstrates Significant Metabolic Benefits
CATALYST screened 1,057 patients with difficult-to-control type 2 diabetes (HbA1c 7.5–11.5% despite multiple glucose-lowering agents). Hypercortisolism was identified in 24% of patients using the standard 1-mg dexamethasone suppression test.
In the randomized treatment phase (n=136, 2:1 Korlym versus placebo, 24 weeks), Korlym achieved a statistically significant 1.3% reduction in HbA1c (p<0.001), alongside clinically meaningful reductions in body weight (-5.1 kg), BMI (-1.7 kg/m²), and waist circumference (-5.1 cm). The primary treatment-phase findings were previously published in Diabetes Care in 2025.
A focused ADA analysis of 71 participants already receiving GLP-1 receptor agonists or tirzepatide showed even greater improvements. Patients treated with Korlym experienced HbA1c reductions of 1.7%, weight loss of 6.1 kg, BMI reductions of 2.0 kg/m², and waist circumference decreases of 6.5 cm compared with placebo. All outcomes achieved nominal p-values below 0.04, underscoring cortisol’s independent role in metabolic dysfunction.
The most common adverse events included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness.
MOMENTUM Highlights Widespread Underdiagnosis
The MOMENTUM study (NCT06829537) screened 1,086 patients with resistant hypertension across 50 U.S. centers. Hypercortisolism was identified in 27.3% of participants using the same dexamethasone suppression testing approach.
Prevalence was even higher among patients with both resistant hypertension and poorly controlled diabetes. Hypercortisolism was identified in 36.6% of eligible patients in CATALYST and 32.6% of patients in MOMENTUM who had HbA1c levels of at least 7.5% while receiving three or more antihypertensive medications.
Clinical Implications
These findings highlight hypercortisolism as an overlooked contributor to persistent cardiometabolic disease, even in patients treated with advanced therapies such as semaglutide and tirzepatide. The data suggest that routine cortisol screening could identify patients who may benefit from cortisol-directed treatment, potentially improving outcomes in populations that remain difficult to manage with current standards of care.
Future Outlook
The findings add to growing evidence that endogenous hypercortisolism is more common than previously recognized in patients with difficult-to-control diabetes and resistant hypertension. The results may support broader use of dexamethasone suppression testing in high-risk cardiometabolic populations and further evaluation of cortisol-directed therapies as part of a more personalized approach to managing resistant metabolic disease.
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About the Writer
Meghana Jinka (LinkedIn) is a Pharm.D graduate with a strong interest in clinical pharmacy, clinical research, pharmacovigilance, and medical writing. She has developed expertise in evaluating scientific literature, interpreting clinical data, and communicating complex medical information in a clear and accessible manner. Through clinical training, patient counseling, and healthcare awareness activities, she has gained practical experience in evidence-based medicine and patient-centered care. Passionate about healthcare communication, Meghana is committed to developing accurate, engaging, and evidence-based healthcare documents that support healthcare professionals and the wider community.