CurrentBlue Cross Blue Shield - IowaPolicy 05.02.84

Korlym (mifepristone) for hyperglycemia secondary to endogenous Cushing's syndrome

Defines medical necessity criteria, documentation and prior authorization requirements, continuation criteria, dosing limits, and quantity limits for Korlym (mifepristone) for adults with endogenous Cushing's syndrome and associated type 2 diabetes or glucose intolerance.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyKorlym (mifepristone) for hyperglycemia secondary to endogenous Cushing's syndrome

Policy CodePolicy 05.02.84

Change TypeRevised

Effective DateMar 7, 2025

Next Review Date

Key ActionSubmit diagnostic test results confirming Cushing syndrome, documentation of inadequate glycemic control, prior surgery failure or contraindication, prior trials/contraindications to listed oral therapies, and ensure endocrinology involvement and pregnancy testing when applicable.

SourceLink

POLICY UPDATE CHANGES

Policy reviewed January 2026; current effective date March 7, 2025 with prior revisions noted (January 2025).

1Covered Indications (FDA-approved)

4Required alternative oral therapies before approval

4Max 300 mg tablets per day

Coverage Summary

Korlym (mifepristone) is covered with criteria for adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and who have failed surgery or are not surgical candidates, consistent with the FDA-approved indication. Coverage requires meeting documented medical necessity criteria (diagnosis confirmation, inadequate glycemic control despite individualized management, surgical non-curative or contraindication, endocrinology involvement, pregnancy testing when applicable, and prior trial/contraindications to listed oral therapies). Key safety monitoring highlights include surveillance for adrenal insufficiency, hypokalemia, and prolongation of the QT interval, and exclusion of pregnancy with counseling on use of nonhormonal contraception during treatment and for 1 month after stopping therapy.

Initial Therapy Criteria

Criteria for Initial Approval

Korlym (mifepristone) may be considered medically necessary when ALL of the following are met:

ALL of the following

Member has type 2 diabetes mellitus or glucose intolerance
A confirmed diagnosis of hyperglycemia secondary to hypercortisolism in an individual with endogenous Cushing's syndrome
Member has failed to achieve adequate glycemic control despite individualized diabetic management
ANY of the following
- Surgery to remove the causative tumor did not result in normalization of circulating cortisol levels and associated glucose intolerance
- Surgical removal is contraindicated, or member is not a candidate for surgery
If the member is able to become pregnant, a negative pregnancy test is required before initiating therapy
Prescribed by, or in consultation with, a board-certified endocrinologist
ALL of the following
- ketoconazole
- cabergoline
- metyrapone
- mitotane

Documentation required for Initial Requests

Submission of the following information is necessary to initiate the prior authorization review:

ALL of the following

Diagnostic test results confirming diagnosis of Cushing Syndrome including but not limited to late-night salivary cortisol (two measurements), urine free cortisol (UFC; at least two measurements), overnight 1 mg dexamethasone suppression test (DST) or longer low-dose (2 mg/day for 48 hrs) DST
Documentation supporting inadequate glycemic control and diagnosis of Type 2 diabetes or impaired glucose tolerance/pre-diabetes by fasting plasma glucose, an oral glucose tolerance test, and/or hemoglobin A1c
ALL of the following
- Surgery to remove the causative tumor did not result in normalization of circulating cortisol levels and associated glucose intolerance
- Surgical removal is contraindicated, or member is not a candidate for surgery

Continuation of Therapy Criteria

Criteria for Continuation of Therapy

Korlym may be considered medically necessary for continued treatment when ALL of the following are met:

ALL of the following

The member has experienced a positive clinical benefit to therapy defined as achieving and maintaining improved glycemic control as evidenced by a documented decrease in hemoglobin A1C levels and blood glucose levels
The member continues to be seen by an endocrinologist or is in consultation with an endocrinologist

Provider Actions & Prior Authorization

Prior Authorization

Prior authorization and documentation required

Submit diagnostic test results confirming Cushing syndrome (examples listed below), documentation of inadequate glycemic control (FPG, OGTT, and/or A1c), documentation that surgery was non-curative or is contraindicated/not an option, and documentation of prior trials or contraindications to listed oral therapies (ketoconazole, cabergoline, metyrapone, mitotane).

Late‑night salivary cortisol (two measurements)
Urine free cortisol (UFC; at least two measurements)
Overnight 1 mg dexamethasone suppression test or longer low‑dose (2 mg/day for 48 hrs) DST
Fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and/or hemoglobin A1c

Documentation Required

Pregnancy testing requirement

Obtain a negative pregnancy test before initiating Korlym for anyone able to become pregnant and counsel on use of nonhormonal contraception during treatment and after stopping therapy.

Use nonhormonal contraception during treatment and for 1 month after stopping therapy

Documentation Required

Specialist involvement

Korlym must be prescribed by, or in consultation with, a board-certified endocrinologist. For continuation, the member must continue to be seen by an endocrinologist or be in consultation with one and documentation must show ongoing clinical benefit (improved and maintained glycemic control).

Ongoing endocrinology follow-up or documented consultation required for continuation

Billing Rule

Dosing and quantity limit enforcement

Approvals may be subject to dosing limits per FDA labeling and evidence‑based guidelines; quantity limits are enforced per policy.

Quantity limit = 4 x 300 mg tablets per day

Denial Risk

Denial if criteria not met

Requests missing the required diagnostic documentation, evidence of prior surgical failure or contraindication, endocrinology involvement, a pregnancy test when applicable, or documentation of prior trials/contraindications to the listed alternative oral therapies may be denied as not medically necessary.

Clinical Evidence

The primary efficacy evidence is a 24-week, uncontrolled, multicenter, open-label trial of 50 patients (diabetes and hypertension cohorts) in which the diabetes cohort had a mean HbA1c reduction of 1.1% and 60% of patients met the study's primary glucose endpoint. Adverse events were reported in 88% of patients; the most common included nausea (48%), fatigue (48%), headache (44%), hypokalemia (34%), and arthralgia (30%). Clinical guidelines from the Endocrine Society recommend mifepristone for patients with diabetes or glucose intolerance who are not surgical candidates or who have persistent disease after surgery.

Background & Definitions

Korlym (mifepristone) is a glucocorticoid receptor antagonist (antiprogestational agent at high doses) FDA-approved to control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. The policy aligns coverage with FDA labeling and guideline recommendations and requires appropriate diagnostic documentation and specialist involvement. Safety monitoring emphasized in the labeling and policy includes observation for adrenal insufficiency, monitoring and management of hypokalemia, assessment for QT interval prolongation, and strict pregnancy precautions (exclude pregnancy before initiation and require nonhormonal contraception during treatment and for 1 month after discontinuation). The policy also notes a quantity limit of 4 Korlym 300 mg tablets per day in accordance with dosing limits.

Term	Definition
Hypercortisolism secondary to endogenous Cushing's syndrome	Excess cortisol production due to ACTH-producing pituitary tumor, ectopic ACTH secretion, or adrenal adenoma/carcinoma causing hyperglycemia and other clinical features.

Revision History

December 20, 2019revised

Original effective date listed as December 20, 2019.

January 2025revised

Policy revised January 2025 (prior revision noted).

March 7, 2025revisedLatest

Current effective date March 7, 2025; policy text reviewed and effective as of this date.

January 2026reviewed

Policy reviewed January 2026.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyKorlym (mifepristone) for hyperglycemia secondary to endogenous Cushing's syndrome

Policy CodePolicy 05.02.84

Change TypeRevised

Effective DateMar 7, 2025

Next Review Date

SourceLink

On This Page

OpenPayer

Korlym (mifepristone) for hyperglycemia secondary to endogenous Cushing's syndrome

Coverage Summary

Initial Therapy Criteria

Continuation of Therapy Criteria

Not Medically Necessary / Exclusions

Provider Actions & Prior Authorization

Applicable Codes

Clinical Evidence

Background & Definitions

Revision History