(P103) Final Results of the CATALYST Trial

This poster reviews CATALYST Part 1, which showed that endogenous hypercortisolism is present in 24% of individuals with difficult-to-control type 2 diabetes (T2D), defined as HbA1c 7.5% to 11.5% on multiple glucose-lowering medications. CATALYST Part 2 evaluated the efficacy and safety of mifepristone, a glucocorticoid receptor antagonist, in individuals with difficult-to-control T2D and hypercortisolism (cortisol >1.8 μg/dL on a 1-mg dexamethasone suppression test with dexamethasone ≥140 ng/dL). In this prospective double-blind, phase 4 study, participants were randomized 2:1 to mifepristone (300-900 mg/day; n=91) or placebo (n=45) for 24 weeks, stratified by the presence/absence of adrenal imaging abnormality. Mifepristone significantly decreased HbA1c from baseline to week 24 (least-squares mean [LSM] change, -1.47%) vs placebo (placebo-adjusted LSM difference, -1.32% [95% CI, -1.81 to -0.83]; P<0.0001), despite many participants in the mifepristone group reducing or discontinuing glucose-lowering medications. Mifepristone also significantly decreased body weight and waist circumference vs placebo (placebo-adjusted LSM difference, -5.1 kg [95% CI, -8.20 to -2.03] and -5.1 cm [95% CI, -8.23 to -1.99], respectively; both P<0.01). Common (>10%) adverse events with mifepristone were consistent with those previously described, including hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness. This study supports the need to consider evaluating and addressing hypercortisolism in this patient population.