At last year’s Scientific Sessions, investigators shared findings from the first phase of the CATALYST trial, demonstrating the prevalence of hypercortisolism in people with difficult-to-manage type 2 diabetes. They return this year to present findings from phase 2 of the trial, in which they studied the efficacy and safety of the glucocorticoid receptor modulator mifepristone in treating this challenging patient population.

The symposium, Treatment of Hypercortisolism in People with Difficult-to-Control Type 2 Diabetes—Final Results of the CATALYST Trial, will be held on Monday, June 23, from 3:15–4:15 p.m., in Room W375 A of the McCormick Place Convention Center. On-demand access to recorded presentations will be available to registered participants following the conclusion of the 85^th Scientific Sessions, from June 25–August 25.

“In phase 1 of CATALYST, we looked at 1,000 people who had uncontrolled diabetes and were on at least three diabetes medications, or were on insulin plus one other medication, or they had coexistent difficult-to-control diabetes on two diabetes drugs and a microvascular or macrovascular complication,” said Vivian Fonseca, MD, Professor of Medicine and Pharmacology, Chief of the Section of Endocrinology, and Assistant Dean for Clinical Research at Tulane University School of Medicine. “After an overnight dexamethasone suppression test, we were surprised to find that 24% of people who were difficult to control did not suppress to 1.8 mcg/dL or lower.”

Previous studies in Europe suggested that people who did not suppress to ≤1.8 mcg/dL tended to have more medical problems and perhaps higher mortality, Dr. Fonseca said.

“So, in phase 2 of CATALYST, which was pre-planned, we took those people who were abnormal in their cortisol suppression and offered them the opportunity of participating in a randomized trial of a specific treatment—mifepristone—that blocks cortisol or placebo,” he said.

Dr. Fonseca will present the complete CATALYST phase 2 results at the 85^th Scientific Sessions. Among those findings, Dr. Fonseca said that patients in the treatment group saw their A1C levels drop by a more significant amount than those of patients in the placebo group.

This, and other findings from the trial, suggest a potential new paradigm in the understanding and treatment of people with difficult-to-manage type 2 diabetes, according to John B. Buse, MD, PhD, the Verne S. Caviness Distinguished Professor of Medicine, Director of the Diabetes Care Center, and Director of the Translational and Clinical Sciences Institute at the University of North Carolina at Chapel Hill. Dr. Buse will outline the potential implications of the insights from CATALYST for clinical care.

“The key implication is that if people are poorly controlled or inadequately controlled despite best efforts on the part of the patient and the provider, they should have an overnight dexamethasone suppression test. Our study shows that nearly a quarter of them have hypercortisolism. If that test is positive, they should be referred to an endocrinologist with experience in using therapies to reduce either the synthesis and secretion of cortisol or the action of cortisol,” Dr. Buse said. “Mifepristone may not be the ideal solution to the problem, but we now have evidence that it is effective for many. There is now adequate data to support a paradigm shift in diabetes care to screen for and treat hypercortisolism as an approach to improve glycemic control in many with previously uncontrolled type 2 diabetes based on the full results of the CATALYST study.”

Dr. Fonseca said this represents a precision approach to treating diabetes: Do a simple test to detect an abnormality, then choose a treatment that is specific in addressing that abnormality.

Joining Dr. Fonseca and Dr. Buse for the symposium will be Vanita R. Aroda, MD, Director of Diabetes Clinical Research, Brigham and Women’s Hospital, who will describe the rationale and design of the CATALYST trial; and Ralph A. DeFronzo, MD, Professor of Medicine, Chief of the Diabetes Division, and Deputy Director of the Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, who will discuss the growing evidence for the impact of hypercortisolism on people with difficult-to-manage type 2 diabetes.