The CATALYST trial has identified hypercortisolism as a significant factor affecting diabetes management, offering new treatment possibilities for approximately 1.2 to 1.3 million poorly controlled diabetes patients in the United States.
Key Insights from the CATALYST Trial:
At the American Diabetes Association’s Scientific Sessions, the CATALYST trial highlighted a crucial discovery in diabetes management: hypercortisolism is a significant factor in poorly controlled diabetes. The study found that excess cortisol, which can induce insulin resistance, increase liver glucose production, and impair beta cell function, plays a vital role in making diabetes management challenging.
Dr. Ralph A. DeFronzo, professor of medicine at UT Health San Antonio, emphasized that addressing hypercortisolism through surgical removal of adrenal adenomas or using medications such as mifepristone (Korlym; Corcept Therapeutics), a glucocorticoid receptor antagonist, could potentially enhance glucose tolerance and blood pressure control in these patients. Ongoing research, including the second phase of the CATALYST study and the GRAY study with relacorilant (Corcept Therapeutics), aims to delve deeper into these treatments’ effectiveness while monitoring potential adverse events.
Scope of the Issue:
In the United States, approximately 40 million individuals have type 2 diabetes, with about 25% having poorly controlled diabetes (hemoglobin A1c above eight). Among these 10 million patients, half are on multiple oral agents with or without insulin, yet still struggle to control their condition. The CATALYST trial identified that 24% of this subgroup, roughly 1.2 to 1.3 million people, suffer from hypercortisolism, a condition that has been overlooked as a contributor to their poor diabetes control.
Understanding Hypercortisolism’s Impact:
Cortisol contributes significantly to diabetes-related issues by causing insulin resistance in muscles and the liver, increasing liver glucose production, and impairing beta cell function. These effects exacerbate the already present genetic defects in diabetic patients, making glucose control difficult.
Potential Treatments:
Identifying hypercortisolism as a key factor opens new treatment avenues. Imaging studies can determine if patients have adrenal adenomas, which can be surgically removed. For those without adenomas, mifepristone (Korlym) offers a promising alternative by blocking cortisol’s interaction with its receptor, thus mitigating its adverse effects.
The ongoing second phase of the CATALYST study is assessing the efficacy of mifepristone in improving glucose tolerance and blood pressure control. While effective, mifepristone can cause side effects, such as endometrial thickening and vaginal bleeding in women, due to its interference with the progesterone receptor.
Future Directions:
The GRAY study, focusing on relacorilant (Corcept Therapeutics), a drug specific to the glucocorticoid receptor without affecting the progesterone receptor, presents an alternative with fewer side effects. Initial results are promising, indicating that future treatments could potentially avoid the adverse effects associated with mifepristone.
Conclusion:
The CATALYST trial’s findings underscore the importance of considering hypercortisolism in the management of poorly controlled diabetes. With ongoing research and the development of more targeted treatments, there is hope for improved management and outcomes for this significant patient population.
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