Can Korlym (mifepristone) be used to treat diabetes insipidus?

Korlym (Mifepristone) is Not Indicated for Diabetes Insipidus Treatment

Korlym (mifepristone) is not indicated or recommended for the treatment of diabetes insipidus, as there is no evidence supporting its efficacy for either central or nephrogenic diabetes insipidus. 1, 2

Understanding Diabetes Insipidus Types and Management

Diagnosis and Classification

• Diabetes insipidus (DI) should be suspected in patients with polyuria, polydipsia, and inappropriately dilute urine (urine osmolality <200 mOsm/kg H₂O) with high-normal or elevated serum sodium 1, 2
• There are two main types of diabetes insipidus:
  • Central DI: Caused by insufficient production of vasopressin (AVP) 2, 3
  • Nephrogenic DI: Caused by kidney resistance to vasopressin action 1, 2
• Genetic testing is strongly recommended for suspected nephrogenic diabetes insipidus to confirm diagnosis 1, 2

Evidence-Based Treatment Approaches for Diabetes Insipidus

For Central Diabetes Insipidus:

• Desmopressin (synthetic vasopressin analog) is the cornerstone of treatment for central DI 3, 4
• Oral desmopressin has largely replaced nasal formulations as a more reliable mode of treatment for chronic central DI 4
• Careful monitoring for hyponatremia is essential, as it occurs in approximately 25% of patients on desmopressin 4

For Nephrogenic Diabetes Insipidus:

• Thiazide diuretics combined with a low-salt diet are recommended as first-line treatment, which can reduce diuresis by up to 50% in the short term 1, 2
• Prostaglandin synthesis inhibitors (COX inhibitors) are often used in combination with thiazides 1
• Amiloride should be added to thiazide therapy in patients who develop hypokalemia 1, 2
• Dietary modifications including low salt (≤6 g/day) and protein restriction (<1 g/kg/day) help reduce renal osmotic load and minimize urine volume 2

Why Korlym is Not Used for Diabetes Insipidus

• Korlym (mifepristone) is a glucocorticoid receptor antagonist that is not mentioned in any current guidelines for diabetes insipidus management 1, 2, 5
• The mechanism of action of mifepristone does not address the underlying pathophysiology of either central or nephrogenic diabetes insipidus 3, 5
• Current guidelines from Nature Reviews Nephrology and other authoritative sources do not include mifepristone in their treatment recommendations for any form of diabetes insipidus 1, 2

Important Monitoring Considerations in Diabetes Insipidus

• Regular assessment of height and weight, especially in children with DI 1, 2
• Monitoring of basic plasma parameters (Na, K, Cl, HCO₃, creatinine, osmolality) and urine osmolality 2
• Kidney ultrasound should be performed at least once every 2 years to monitor for urinary tract dilatation in patients with chronic DI 2
• Each patient with DI should have an emergency plan, including a letter explaining their diagnosis with advice regarding intravenous fluid management 2

Practical Considerations for Clinicians

• Free access to fluid is essential in all patients with diabetes insipidus to prevent dehydration and hypernatremia 2
• When fasting is required (>4h), intravenous 5% dextrose in water at maintenance rate with close monitoring is recommended 2
• Close observation of clinical status, including neurological condition, fluid balance, body weight, and serum electrolytes, is crucial during acute management 2, 5

Conclusion

When treating diabetes insipidus, clinicians should follow evidence-based guidelines that recommend desmopressin for central DI and thiazide diuretics with prostaglandin synthesis inhibitors for nephrogenic DI. Korlym (mifepristone) has no established role in the management of either form of diabetes insipidus.