Rapid Clinical Improvements in a Patient with Difficult-to-Control Type 2 Diabetes by Addressing Underlying Hypercortisolism with Mifepristone

Conclusions and Takeaways

This case presents a patient with long-standing (40+ years) difficult-to-control T2D (HbA1c: 8.7%, CGM TIR: 33%, GMI [CGM-based A1c estimate]: 8.3%, mean glucose: 208 mg/dL) and multiple comorbidities (treatment-resistant hypertension, morbid obesity) that could not be effectively managed despite long-term, extensive medical interventions.
Hypercortisolism was suspected due to the patient’s multiple comorbidities and confirmed through biochemical assessment and imaging.
The patient was treated with mifepristone, a competitive glucocorticoid receptor antagonist, for 4 months, during which he experienced substantial weight loss of 34.4 lbs (310.4 lbs to 276.0 lbs), improvement in glycemic control (at 2 months [CGM TIR: 91%, GMI: 6.6%] and 4 months [CGM TIR: 47%, GMI: 7.8%]) with reduction of insulin from U500 to U100 at 3 months, and discontinuation/reduction in 5 of 7 antihypertensive medications.
Upon discontinuation of mifepristone, due to unrelated orthostatic hypotension, the patient’s glycemic control deteriorated (at 3 months [CGM TIR: 5%, GMI: 10.2%] and 6 months [CGM TIR: 31%, GMI: 8.4%] after discontinuation), despite increased use of insulin at 2 months.
This case emphasizes the vital importance of promptly identifying and addressing hypercortisolism in patients with challenging metabolic derangements. Failure to do so resulted in a worsening clinical picture for this patient, which was ameliorated with mifepristone by addressing the underlying hypercortisolism.

T2D, type 2 diabetes; HbA1c, hemoglobin A1c; CGM, continuous glucose monitor; TIR, time-in-range; GMI, glucose management indicator (CGM-based A1c estimate).