Diabetes Dialogue: Updates in Management of Hypercortisolism in Type 2 Diabetes

The world of diabetes management has undergone a renaissance in recent years. Much of this is driven by interest and development of non-insulin medications for the management of type 2 diabetes. Although the conversation in this arena is dominated by use of GLP-1 receptor agonists to manage body weight or SGLT2 inhibitors for mitigating cardiorenal risk, a considerable amount of focus has been paid to management of other comorbidities, including hypercortisolism.

When discussing hypercortisolism, or Cushing syndrome, many clinicians conjure an image of a woman the medical community has come to know as “Minnie G”. This woman, whose physical appearance is characterized by rosy cheeks, cervicodorsal lipodystrophy, and striae, was a 23-year-old patient examined in 1910 by Harvey Cushing. Although Minnie G is what some might expect a patient with hypercortisolism to present as, Ralph DeFronzo, MD, chief of the Diabetes Division and professor of medicine at UT Health San Antonio, suggests this may not be the case for patients in contemporary settings and this mischaracterization contributes, in part, to the underrecognition of hypercortisolism in patients with type 2 diabetes.¹

Creator of the Ominous Octet, a group of 8 different defects contributing to impaired sugar metabolism, DeFronzo is part of the investigatory team conducting the phase 4 CATALYST trial. Initiated by Corcept Therapeutics in 2023, CATALYST was designed as a 2-part trial, with the first part aimed at assessing the prevalence of hypercortisolism in type 2 diabetes despite receiving standard of care therapies and the second part aimed at assessing the tolerability, safety, and efficacy of treatment with the competitive glucocorticoid receptor antagonist mifepristone (Korlym) in these patients.^2,3

In this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, sat down with DeFronzo to discuss the latest updates in hypercortisolism and how the phase 4 CATALYST trial might influence future management of the condition.

Relevant disclosures for Dr. DeFronzo include Corcept Therapeutics, AstraZeneca, Novo Nordisk, Alynylam Pharmaceuticals, and others. Relevant disclosures for Dr. Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Dr. Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

1. Lanzino G, Maartens NF, Laws ER Jr. Cushing's case XLV: Minnie G. J Neurosurg. 2002;97(1):231-234. doi:10.3171/jns.2002.97.1.0231
2. Frias JP, Auchus RJ, Bancos I, et al. FRI183 Phase 4 Study Of Hypercortisolism In Patients With Difficult-to-Control Type 2 Diabetes Despite Receiving Standard-of-Care Therapies: Prevalence And Treatment With Mifepristone. J Endocr Soc. 2023;7(Suppl 1):bvad114.178. Published 2023 Oct 5. doi:10.1210/jendso/bvad114.178
3. Corcept Therapeutics. Corcept Therapeutics initiates catalyst clinical trial. Corcept Therapeutics. March 28, 2023. Accessed January 9, 2024. https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-initiates-catalyst-clinical-trial.