Findings from the prevalence phase of Corcept Therapeutics' CATALYST trial have been published in Diabetes Care, revealing that 24 percent of patients with difficult-to-control type 2 diabetes have hypercortisolism, also known as Cushing's syndrome. This groundbreaking study represents the largest and most rigorous investigation ever conducted to assess the prevalence of this condition in this specific patient population.
The CATALYST trial screened 1,057 patients at 36 sites across the United States. All participants had hemoglobin A1c levels greater than 7.5 percent despite receiving multiple glucose-lowering therapies, including GLP-1 receptor agonists. Using a standardized 1-mg dexamethasone suppression test (DST), researchers identified hypercortisolism in nearly one-quarter of these patients.
"Many patients have uncontrolled type 2 diabetes despite the use of the best available medications," said lead author John Buse, M.D., Ph.D., director of the University of North Carolina's Diabetes Center. "It is critical for clinicians to consider and address all factors that can contribute to inadequate glucose control. CATALYST's results show that, for many patients, hypercortisolism is one of those factors."
Clinical Implications for Diabetes Management
The findings suggest that screening for hypercortisolism should be considered in patients whose diabetes remains poorly controlled despite optimal therapy. The simple dexamethasone suppression test used in the study could potentially become part of the diagnostic workup for patients with treatment-resistant diabetes.
Bill Guyer, PharmD, Corcept's Chief Development Officer, emphasized the significance of these results: "CATALYST provides valuable insights into an often-unrecognized cause of difficult-to-control type 2 diabetes. These prevalence data, in combination with data from the treatment phase of the study, will hopefully help patients with hypercortisolism receive the diagnosis and care they need."
Treatment Phase Shows Promise
The second part of the CATALYST trial—a randomized, double-blind, placebo-controlled study of Korlym® (mifepristone) in patients with hypercortisolism and difficult-to-control type 2 diabetes—has already demonstrated positive outcomes. According to Corcept Therapeutics, this phase met its primary endpoint of reduction in hemoglobin A1c.
Topline results were announced in December 2024, with complete findings scheduled for presentation at the American Diabetes Association's 85th Scientific Sessions on June 23, 2025. The presentation will be titled "Treatment of Hypercortisolism in People with Difficult-to-Control Type 2 Diabetes – Final Results of the CATALYST Trial."
Understanding Hypercortisolism
Hypercortisolism is caused by excessive activity of the hormone cortisol. The condition manifests through various symptoms, including hypertension, central obesity, elevated blood sugar, difficult-to-control type 2 diabetes, severe fatigue, and muscle weakness. Patients may also experience irritability, anxiety, depression, and cognitive disturbances.
If left untreated, hypercortisolism can affect every organ system and may be lethal. The condition has historically been challenging to diagnose due to the overlap of its symptoms with common metabolic disorders.
About Corcept Therapeutics
For over 25 years, Corcept Therapeutics has focused on cortisol modulation and its potential to treat patients with various serious disorders. The company has discovered more than 1,000 proprietary selective cortisol modulators and glucocorticoid receptor antagonists.
In February 2012, Corcept introduced Korlym®, the first medication approved by the U.S. Food and Drug Administration for treating patients with endogenous hypercortisolism. The company continues to conduct advanced clinical trials in patients with hypercortisolism, solid tumors, ALS, and liver disease.
The publication of the CATALYST trial's prevalence phase represents a significant advancement in understanding the relationship between hypercortisolism and difficult-to-control type 2 diabetes. As the complete results from the treatment phase become available, they may reshape clinical approaches to managing treatment-resistant diabetes by highlighting the importance of screening for and addressing underlying hormonal imbalances.
