Mifepristone improved diabetes control in hypercortisolism, industry trial finds

Patients with hypercortisolism and poorly controlled type 2 diabetes may benefit from mifepristone therapy, according to a recent industry-funded study.

Researchers randomized 136 patients with poorly controlled type 2 diabetes (defined as an HbA1c level of 7.5% to 11.5% on multiple medications) and hypercortisolism (as determined by a dexamethasone suppression test) in a 2:1 ratio to mifepristone or placebo for 24 weeks. The study's primary end point was change in HbA1c level, while secondary end points included safety and changes in glucose-lowering medications, weight, and waist circumference. Corcept Therapeutics funded the study and provided editorial support. The results were published June 23 by Diabetes Care.

The trial was conducted at 36 sites in the U.S. Ninety-one patients were assigned to mifepristone, 300 to 900 mg once daily, and 24 were assigned to placebo. Patients' mean age was 63.2 years, 39% were female, and 80.9% identified as White. The mean HbA1c level at baseline was 8.55%. At 24 weeks, the least squares mean (LSM) difference in HbA1c level from placebo was −1.32% (95% CI, −1.81% to −0.83%; P<0.001), and body weight and waist circumference decreased in the mifepristone group (placebo-adjusted LSM differences, −5.12 kg [95% CI, −8.20 kg to −2.03 kg] and −5.1 cm [−8.23 cm to −1.99 cm], respectively).

Forty-six percent of those in the mifepristone group discontinued therapy versus 18% in the placebo group, with most withdrawals due to adverse events (61.9% vs. 37.5%, respectively). Adverse events reported in the mifepristone group included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness. Increased blood pressure was also seen in the mifepristone group.

Limitations include the study's small size, the inclusion of mostly White patients, and the number of adverse events, the authors noted.

“In conclusion, individuals with [type 2 diabetes] who appear resistant to conventional glucose-lowering therapies should be considered for screening for hypercortisolism, which is amenable to cortisol-directed therapy with mifepristone that may lead to reduced HbA1c,” they wrote. “The tolerability profile of mifepristone was manageable, though the rate of adverse events and discontinuations was higher than in the placebo arm in this study. Longer-term studies are needed to demonstrate the benefits of treating hypercortisolism for other clinical outcomes.”