Mifepristone Significantly Lowers HbA1c in Type 2 Diabetes with Hypercortisolism: Study
Researchers have discovered in a randomized placebo-controlled trial that mifepristone (Korlym) led to a significant reduction in HbA1c levels in patients with poorly controlled type 2 diabetes and hypercortisolism. The findings of the study were presented at the ADA annual meeting. The study was published in Diabetes Care by Ralph A. and colleagues.
Hypercortisolism, a frequently underappreciated cause of inadequate glycemic control, occurred in most patients in spite of being on several diabetes medications. Aiming to intervene on the glucocorticoid receptor, investigators sought to determine whether controlling cortisol action could enhance diabetic outcomes in cases where conventional treatment has not succeeded.
The study enrolled 136 participants aged 18 or older with established type 2 diabetes (HbA1c between 7.5% and 11.5%, equivalent to 58–102 mmol/mol) who were already on multiple glucose-lowering medications but had inadequate glycemic control. All participants demonstrated biochemical evidence of hypercortisolism based on dexamethasone suppression testing. Subjects were randomized in a 2:1 ratio to receive either mifepristone (91 participants) or placebo (45 participants) once daily for 24 weeks. Stratification was according to whether or not participants had an abnormality on adrenal imaging.
Key Findings
• At baseline, mean HbA1c in the total cohort was 8.55% (69.9 mmol/mol). At 24 weeks of treatment:
• The mifepristone arm had a placebo-adjusted decrease in HbA1c of −1.32% (95% CI: −1.81 to −0.83; P < 0.001), indicating substantial glycemic improvement.
• Patients who were given mifepristone lost a mean of 5.12 kg (95% CI: −8.20 to −2.03) body weight and 5.1 cm waist circumference (95% CI: −8.23 to −1.99).
• In the users of mifepristone, 46% stopped therapy, primarily because of adverse effects, as was 18% in the placebo group.
• Nineteen participants had an adverse event.
• Common side effects occurring in over 10% of participants on mifepristone were hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness.
• There were also increases in blood pressure among some participants, which is in agreement with the established pharmacological profile of the drug.
Among patients with poorly controlled type 2 diabetes and biochemical hypercortisolism, mifepristone treatment for 24 weeks substantially decreased HbA1c, body weight, and waist size. In spite of a significant frequency of therapy discontinuation because of side effects, the tolerability profile was as expected for the drug.
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