Evolving Treatment Paradigms in Hypercortisolism: Integrating Emerging Evidence into Practice - Episode 7
Mifepristone in Hypercortisolism and Difficult-to-Control Diabetes: Key Findings From the CATALYST Study’s Treatment Phase
Panelists discuss how the CATALYST study’s treatment phase results demonstrated that mifepristone significantly reduced hemoglobin A1C (HbA1C) level by 1.45% in patients with hypercortisolism and difficult-to-control diabetes while also reducing waist circumference and managing blood pressure effects.
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The CATALYST study’s treatment phase represents a significant advancement in precision diabetes management, involving approximately 1000 participants in phase 1 to determine hypercortisolism prevalence. Of these patients, 24% had positive results on dexamethasone suppression testing, with a subset participating in a randomized, double-blind, placebo-controlled trial using a 2:1 treatment to placebo ratio. The study’s primary end point focused on HbA1C reduction over 24 weeks, with secondary end points including weight loss, waist circumference reduction, and blood pressure management.
The treatment results demonstrated remarkable efficacy in this difficult-to-control diabetes population. Patients receiving mifepristone achieved a substantial 1.45% HbA1C reduction from a baseline of 8.5% compared with only 0.15% improvement in the placebo group. Importantly, this improvement occurred despite many patients reducing or discontinuing other diabetes medications, including fast-acting insulin, sulfonylureas, and some glucagon-like peptide-1 receptor agonists. The study results also showed significant waist circumference reduction that was disproportionate to overall weight loss, indicating targeted visceral fat reduction.
Blood pressure responses varied based on baseline values, with an interesting finding that patients with blood pressure above 130 mm Hg maintained stable readings whereas those with lower baseline pressures experienced modest increases that remained within normal ranges. This pattern is attributed to increased mineralocorticoid receptor activation due to rising cortisol levels. The study notably included patients both with and without adrenal abnormalities, showing equivalent HbA1C improvements regardless of anatomical findings, suggesting that functional hypercortisolism rather than structural abnormalities drives metabolic dysfunction.
