Korlym (mifepristone 300 mg) is an FDA-approved oral medication for controlling hyperglycemia (high blood sugar) in adults with endogenous Cushing's syndrome who have Type 2 diabetes or glucose intolerance โ and who are not candidates for surgery or have not had adequate response to surgery. It belongs to a unique class: a glucocorticoid receptor antagonist โ it does not lower cortisol, but blocks cortisol from acting on its receptors.
๐ง Cushing's Syndrome Specialist: Our endocrinologists manage the full spectrum of Cushing's syndrome โ from diagnosis through medication management. Call 832-968-7003 to schedule a consultation.
How Korlym Works โ A Fundamentally Different Approach
Most Cushing's medications work by reducing cortisol production in the adrenal glands (steroidogenesis inhibitors). Korlym takes a completely different approach: it blocks the glucocorticoid receptor, preventing cortisol from binding and exerting its harmful effects on tissues โ even though cortisol levels remain elevated or may even rise.
This distinction has critical implications:
- Cortisol blood levels cannot be used to monitor treatment response โ they will appear elevated even when the drug is working
- Urinary free cortisol (UFC) cannot be used to monitor efficacy
- Treatment response is monitored through clinical symptoms and blood glucose control
- ACTH and cortisol levels rise on therapy (expected โ not a sign of treatment failure)
FDA-Approved Indication
Korlym is specifically approved for Cushing's syndrome patients who have Type 2 diabetes mellitus or glucose intolerance. The primary endpoint in trials was improvement in glucose control โ HbA1c and fasting glucose. It is not approved for all Cushing's syndrome patients; the glycemic indication reflects where it has strongest proven benefit.
Clinical Evidence โ SEISMIC Trial
- ~60% of patients showed significant improvement in glucose tolerance (primary endpoint)
- Mean HbA1c decreased by 1.1% from baseline
- Weight loss averaging ~5.7 kg (12.5 lbs)
- Improvements in blood pressure, quality of life, and physical appearance
- Insulin doses reduced significantly in insulin-dependent patients
Dosing
- Route: Oral tablet, taken once daily with a meal
- Starting dose: 300 mg once daily
- Titration: May be increased by 300 mg increments every 2โ4 weeks based on clinical response, to a maximum of 1,200 mg/day (or 20 mg/kg/day)
- Monitoring: Clinical symptoms, glucose, blood pressure, potassium, adrenal function signs
Key Side Effects & Safety Concerns
| Side Effect | Frequency | Management |
|---|---|---|
| Adrenal insufficiency | Serious risk | Cannot detect with cortisol levels โ monitor for symptoms (fatigue, nausea, hypotension); requires high-dose dexamethasone to treat (not hydrocortisone) |
| Hypokalemia (low potassium) | Very common (~34%) | Potassium supplementation and/or fludrocortisone; monitor regularly |
| Edema (fluid retention) | Common (~26%) | Usually manageable with diuretics if needed |
| Hypertension | Common | Monitor blood pressure; may require antihypertensive adjustment |
| Nausea, fatigue, headache | Common | Usually mild; often improves with time |
| Endometrial thickening | Common in women | Mifepristone blocks progesterone receptors too โ annual or periodic endometrial monitoring required in pre-menopausal and post-menopausal women |
| Vaginal bleeding / irregular periods | Common in women | Expected; monitor and report heavy bleeding |
โ ๏ธ Critical: Adrenal Crisis on Korlym โ Because cortisol is blocked (not reduced), standard cortisol levels cannot diagnose adrenal insufficiency during Korlym therapy. If adrenal crisis is suspected (severe fatigue, vomiting, hypotension, confusion), patients must go to the ER immediately. Treatment requires high-dose dexamethasone โ which bypasses the blocked glucocorticoid receptor. Korlym should be held during any major surgery or serious illness.
Drug Interactions โ REMS Program
Korlym is available only through a Risk Evaluation and Mitigation Strategy (REMS) program due to its risks. Key interactions:
- Strong CYP3A inhibitors (ketoconazole, clarithromycin, grapefruit juice) โ dramatically increase mifepristone levels; avoid or use with great caution
- Simvastatin and lovastatin โ avoid; increased risk of myopathy
- Warfarin โ increased anticoagulant effect; close INR monitoring required
- Contraindicated in pregnancy โ mifepristone causes pregnancy termination (it is also used as an abortifacient at higher doses). Women of reproductive potential must use non-hormonal contraception (hormonal contraception is ineffective because the progesterone receptor is also blocked)
Korlym vs. Recorlev vs. Isturisa
| Drug | Mechanism | Monitors Cortisol? | Approved For |
|---|---|---|---|
| Korlym (mifepristone) | Glucocorticoid receptor blocker | No โ cortisol rises | Cushing's + T2D/glucose intolerance |
| Isturisa (osilodrostat) | 11ฮฒ-hydroxylase inhibitor | Yes โ UFC monitored | Cushing's disease (pituitary) |
| Recorlev (levoketoconazole) | Steroidogenesis inhibitor | Yes โ UFC monitored | Endogenous Cushing's syndrome (adults) |
Key Takeaways
- Korlym blocks the glucocorticoid receptor โ cortisol levels remain high but cannot act on tissues
- Approved specifically for Cushing's syndrome with Type 2 diabetes or glucose intolerance
- Cannot monitor treatment with cortisol or UFC โ response tracked by glucose control and symptoms
- Adrenal crisis requires dexamethasone (not hydrocortisone) โ a critical safety point
- Hypokalemia and endometrial thickening require regular monitoring
- Absolutely contraindicated in pregnancy; non-hormonal contraception required
- Available only through a REMS program
Our Team Treats Adrenal Disorders
All five of our providers evaluate and manage adrenal and endocrine conditions. Book with any member of our team:
Book an Appointment โ or call 832-968-7003