Diabetes Care

ADA 2025: Mifepristone improves glycemic control in inadequately controlled T2DM with hypercortisolism

June 30, 2025

Study details: This prospective, multicenter, double-blind trial randomized 136 adults with inadequately controlled T2DM (HbA1c 7.5% to 11.5% on multiple agents) and confirmed hypercortisolism (by dexamethasone suppression test) to mifepristone (300–900 mg daily, n=91) or placebo (n=45) for 24 weeks. Randomization was stratified by presence or absence of adrenal imaging abnormalities. Primary endpoint was change in HbA1c; secondary endpoints included changes in antidiabetic medications, weight, waist circumference, and safety profile.

Results: At 24 weeks, mifepristone produced a placebo-adjusted least squares mean reduction in HbA1c of 1.32% (95% confidence interval [CI], -1.81 to -0.83; P<0.001). Significant reductions in body weight (-5.1 kg) and waist circumference (-5.1 cm) were also observed. Adverse events were more frequent with mifepristone (46% discontinuation vs. 18% with placebo), with hypokalemia, fatigue, nausea, vomiting, headache, edema, diarrhea, and dizziness being most common. BP increases were also noted.

Clinical impact: Mifepristone may be a valuable adjunct in managing hyperglycemia in patients with T2DM and biochemical hypercortisolism. Consider screening for subtle cortisol excess in patients with refractory diabetes to identify candidates for targeted endocrine therapy.

Source:

DeFronzo RA, et al; CATALYST Investigators. (2025, June 23). Diabetes Care. Inadequately Controlled Type 2 Diabetes and Hypercortisolism: Improved Glycemia With Mifepristone Treatment. https://pubmed.ncbi.nlm.nih.gov/40550011/