Type 2 diabetes remains inadequately controlled for many patients despite treatment with multiple glucose-lowering medications. A subset of these patients shows hypercortisolism, highlighting a potential target for therapy. These findings were presented at the 2025 European Association for the Study of Diabetes (EASD) Annual Meeting.

In this double-blind, phase 4 study, 136 participants with type 2 diabetes and hypercortisolism received either mifepristone 300–900 mg daily (n=91) or placebo (n=45) for 24 weeks in a 2:1 allocation. The primary endpoint was change in HbA1c, with secondary endpoints including weight, waist circumference, and safety.

At 24 weeks, mifepristone significantly reduced HbA1c by 1.47% from baseline compared with placebo (placebo-adjusted difference, -1.32%; 95% CI, -1.81 to -0.83; P<0.0001). Reductions in body weight (-5.1 kg) and waist circumference (-5.1 cm) were also observed. Adverse events were consistent with previous reports and included hypokalemia, fatigue, nausea, and peripheral edema, but no adrenal insufficiency occurred.

The study demonstrates that addressing hypercortisolism with cortisol-directed therapy can meaningfully improve glycemic and metabolic outcomes in patients with difficult-to-treat type 2 diabetes.