Diabetes Dialogue: CATALYST Trial and Hypercortisolism in T2D, with John Buse, MD, PhD

Even with the second half of the trial yet to be completed, results of the CATALYST trial have initiated a potentially seismic shift in discussions around the management of type 2 diabetes.

With the first part of the trial suggesting approximately 1-in-4 patients with difficult-to-control type 2 diabetes, results suggest hypercortisolism could be an underlying driver of suboptimal disease management for millions of people with type 2 diabetes in the US. Now, with this knowledge in hand, the community waits with bated breath for Corcept Therapeutics’ announcement of results from the second half of the trial, which assessed the use of mifepristone (Korlym) by randomizing patients who were diagnosed with hypercortisolism in a 2:1 ratio to mifepristone or placebo therapy.

“I've been doing clinical trials and diabetes since the mid 1990s and, you know, I've been involved in a lot of really amazing stuff in diabetes care over the last 30 years, but this might be the biggest thing that I have ever done in my career,” said principal investigator John Buse, MD, PhD, chief of the Division of Endocrinology and the director of the University of North Carolina’s Diabetes Care Center, when discussing the trial.

Buse and fellow investigators presented full data from the first half of the prevalence trial at the 84th American Diabetes Association Scientific Sessions, which came less than 5 months after Corcept Therapeutics announced topline data from the first part of the trial in February 2024.

The first half of CATALYST was designed to assess the prevalence of hypercortisolism among 1000 patients from 36 study sites. For inclusion in the study, patients needed to have an HbA1c greater than 7.5% despite receiving optimal therapies. Of note, the trial defined optimal therapies for type 2 diabetes as 3 or more antihyperglycemic agents or 2 or taking insulin and other antihyperglycemic agents.

Once identified, participants were required to complete a dexamethasone suppression test. If the values from this test were greater than 1.8 µg/dL and dexamethasone levels were greater than 140 ng/dL, these patients were considered as having hypercortisolism.

Results indicated the prevalence of hypercortisolism among patients with difficult-to-control type 2 diabetes was 24% (n=253 of 1055; 95% CI, 21.4 to 26.7). Buse highlighted 35.4% of those with hypercortisolism were taking 3 or more antihypertensive medications and were more likely to have cardiovascular risk relative to those without hypercortisolism.

Further analysis demonstrated those with hypercortisolism were older, more likely to be on non-Hispanic or Latino ethnicity, more likely to be enrolled based on hypertension or micro/macrovascular complications, be taking newer classes of antihyperglycemic medications, and have greater overall medication burden. Analysis of adrenal imaging abnormality among 203 patients revealed 34% of patients had an adrenal abnormality, with 23% having a unilateral adrenal adenoma and considered possible candidates for surgery.

In this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives, Buse joins hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, for a deep dive into the trial and what it means for practitioners as well as patients with type 2 diabetes. In the episode, Isaacs, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Bellini, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, discuss the trial background, expected prevalence, reaction to results, and the importance of the second part of the trial as the community moves into the future with knowledge of the true prevalence of hypercortisolism in difficult-to-control type 2 diabetes.

Relevant disclosures for Buse include Altimmune, AstraZeneca, Boehringer-Ingelheim, CeQur, Corcept Therapeutics, Eli Lilly, embecta, Moderna, Novo Nordisk, Tandem, Vertex, and others. Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

1. Campbell P. Catalyst raises red flag on hypercortisolism in type 2 diabetes, with Ralph DeFronzo, MD. HCP Live. June 24, 2024. Accessed July 15, 2024. https://www.hcplive.com/view/catalyst-raises-red-flag-on-hypercortisolism-in-type-2-diabetes-with-ralph-defronzo-md.
2. Corcept Therapeutics, Incorporated. Corcept announces preliminary results from prevalence phase of Catalyst Clinical Trial. Corcept Therapeutics, Incorporated. February 15, 2024. Accessed July 15, 2024. https://ir.corcept.com/news-releases/news-release-details/corcept-announces-preliminary-results-prevalence-phase-catalyst.