Findings from the CATALYST study, the largest prospective trial of its kind, suggest that hypercortisolism may be a significant contributing factor in as many as one in four patients with difficult-to-control type 2 diabetes. The findings were presented by a panel of investigators during a late-breaking symposium on Monday, June 24, at the 84^th Scientific Sessions.

CATALYST screened over 1,000 patients with A1C levels of 7.5–11.5 percent despite treatment with multiple standard-of-care diabetes therapies. Researchers used an overnight 1 mg dexamethasone suppression test (DST) to detect hypercortisolism.

“Hypercortisolism was highly prevalent, 24 percent, in these 1,055 CATALYST participants,” said Vivian Fonseca, MD, Tulane University School of Medicine, who reported the main findings from the study. “We identified several baseline characteristics that increased the odds of having hypercortisolism, including race, ethnicity, a higher medication burden for hypertension, lipids, and psychiatric diseases, as well as the presence of cardiovascular disease.”

The symposium Prevalence of Hypercortisolism in Difficult-to-Control Type 2 Diabetes can be viewed on-demand by registered meeting participants on the virtual meeting platform. If you haven’t registered for the 84^th Scientific Sessions, register today to access the valuable meeting content through Aug. 26.

Hypercortisolism was particularly prevalent in CATALYST participants who had uncontrolled diabetes and also took at least three antihypertensive agents. Additionally, Dr. Fonseca reported that abdominal CT scans revealed adrenal abnormalities in about one-third of study participants, with approximately 25% of them having an adrenal tumor, suggesting that surgical intervention could potentially resolve their hypercortisolism and improve diabetes management.

Overall, the CATALYST investigators believe their findings strongly highlight the need for improved hypercortisolism screening and treatment approaches in this patient population.

“Judicious screening for hypercortisolism is appropriate for people with type 2 diabetes whose disease is difficult to control despite best efforts. Screening is not difficult—the DST is easy to perform, and false positives can be readily excluded,” said John B. Buse, MD, PhD, of the University of North Carolina School of Medicine Diabetes Center and Translational and Clinical Sciences Institute and lead author of the study, who discussed the clinical implications of these findings from part 1 of the trial and what investigators hope to learn from part 2, which is currently underway.

Beyond the medical benefit, Dr. Buse said the knowledge that there is a potential secondary cause for difficult-to-control disease may benefit the mental and emotional health of both patients and their providers, who often struggle under the burden and stigma of poor diabetes control.

“I do think we’re on the cusp of a paradigm change. I’m not going to say that the time is today to change all the guidelines, but we’re getting there,” Dr. Buse said. “This is a new paradigm, though, for understanding why type 2 diabetes is so difficult to control in many patients and certainly deserves more study.”

Part 2 of the CATALYST study is a randomized, prospective, placebo-controlled, double-blind multi-center trial that will assess the safety and efficacy of mifepristone treatment in patients with hypercortisolism who have difficult-to-control type 2 diabetes.

“Should part 2 of the CATALYST study demonstrate a benefit for treating hypercortisolism with a glucocorticoid receptor modulator, we will have a proof of concept that identifying and addressing hypercortisolism is a novel path to improving diabetes care,” Dr. Buse said.

Other speakers during the symposium included Richard Auchus, MD, PhD, University of Michigan, who discussed the spectrum of hypercortisolism; Ralph A. DeFronzo, MD, University Texas Health Science Center at San Antonio, who described the pathologic mechanisms of the condition; and Athena Philis-Tsimikas, MD, Scripps Whittier Diabetes Institute, Scripps Health, who discussed the rationale and design of the CATALYST study.