CATALYST Proves Hypercortisolism More Common than Previously Known in Type 2 Diabetes

Data from the CATALYST trial suggests hypercortisolism could be hampering the community’s best efforts at managing difficult-to-control type 2 diabetes. According to new data presented at the 84th American Diabetes Association Scientific Sessions, hypercortisolism was present in 24% of patients with difficult-to-control type 2 diabetes, with prevalence reaching 1 in 3 when limiting their analyses to those receiving 3 or more antihypertensive agents.¹

Billed as the largest study of its kind, the first half of the CATALYST trial uncovered a prevalence of hypercortisolism among patients with difficult-to-control diabetes greater than many on the investigative had expected, with estimates from the trial purporting more than 1 million US adults with difficult-to-control diabetes type 2 diabetes could have hypercortisolism.^1,2

“The investigators were shocked that it was 24% in this study,” remarked lead investigator John Buse, MD, PhD, from the University of North Carolina School of Medicine Diabetes Center and Translational and Clinical Sciences Institute, in a press conference at the ADA 2024. “Among the steering committee, the highest guess based on our review of the literature beforehand of what we might see in the study was 8%.”

A 2-part, phase 4 trial, the first part of CATALYST was aimed at assessing the prevalence of hypercortisolism in type 2 diabetes despite receiving standard of care therapies and the second part is aimed at assessing the tolerability, safety, and efficacy of treatment with the competitive glucocorticoid receptor antagonist mifepristone (Korlym) in these patients. In February 2024, Corcept Therapeutics announced preliminary results from the first 700 patients enrolled prevalence phase of the trial, which indicated 24% of these patients were identified as having hypercortisolism.^1,2,3,4

Per trial design, the first half of CATALYST sought to screen 1000 patients from 36 study sites for hypercortisolism. For inclusion in the study, patients needed to have an HbA1c greater than 7.5% despite receiving optimal therapies. Once identified, 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.^1,2,3,4

At ADA 2024, a group of study investigators, including Buse, presented data full data from the first phase of the CATALYST trial. Initial analysis revealed the true 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).¹

In comparison to those without hypercortisolism, 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. Additionally, patients with hypercortisolism were more likely to have cardiovascular risk and 35.4% were taking 3 or more antihypertensive medications were diagnosed as having hypercortisolism.¹

Analysis of adrenal imaging abnormality among 203 patients revealed 34% of patients had an adrenal abnormality. Of note, 23% with hypercortisolism had a unilateral adrenal adenoma and were considered possible candidates for surgery.¹

In the second half of the trial, which is still ongoing, individuals will be randomized in a 2:1 ratio to receive treatment with mifepristone or placebo. According to Corcept Therapeutics, the second part of the trial is expected to be completed by the end of 2024.^43,4

“These results are significant as they highlight a previously underrecognized factor contributing to the barriers when it comes to managing type 2 diabetes,” Buse added.² “By identifying hypercortisolism in these patients, we can target treatments more effectively and potentially improve their outcomes.”

References:

1. ^{Buse J. Prevalence of Hypercortisolism in Difficult-to-Control Type 2 Diabetes. Presented at: American Diabetes Association (ADA) 84th Scientific Sessions. June 21 - 24, 2024. Orlando, FL.}
2. ^{American Diabetes Association. One in four patients with difficult-to-control type 2 diabetes experience high levels of cortisol. American Diabetes Association Newsroom. June 24, 2024. Accessed June 24, 2024. https://diabetes.org/newsroom/press-releases/one-four-patients-difficult-control-type-2-diabetes-experience-high-levels.}
3. ^{Corcept Therapeutics, Incorporated. Corcept announces preliminary results from prevalence phase of Catalyst Clinical Trial. Corcept Therapeutics, Incorporated. February 15, 2024. Accessed June 24, 2024. https://ir.corcept.com/news-releases/news-release-details/corcept-announces-preliminary-results-prevalence-phase-catalyst.}
4. ^{Corcept Therapeutics, Incorporated. Corcept completes enrollment in phase 4 catalyst trial. Corcept Therapeutics, Incorporated. April 29, 2024. Accessed June 24, 2024. https://ir.corcept.com/news-releases/news-release-details/corcept-completes-enrollment-phase-4-catalyst-trial.}