Korlym improves results for diabetes patients taking GLP-1 drugs
Trial data show treatment lowers blood sugar, promotes weight loss
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Treatment with Korlym (mifepristone) may help lower blood sugar and promote weight loss in people with hard-to-control diabetes and high cortisol levels who are also taking medications targeting GLP-1, according to a new analysis of data from dozens of patients in the CATALYST clinical trial.
Corcept Therapeutics, the company that sells Korlym, presented the new analyses at the American Diabetes Association’s 86th Scientific Sessions, held June 5-8 in New Orleans.
“These new CATALYST data demonstrate the potential of cortisol modulation to improve critical metabolic parameters, even for patients who have poorly controlled type 2 diabetes despite treatment with powerful GLP-1 or GLP-1/GIP receptor agonists, such as semaglutide or tirzepatide,” Lance Sloan, MD, president of the Texas Institute for Kidney and Endocrine Disorders, said in a press release from Corcept. “Excess cortisol disrupts [hormones that control blood sugar and digestion], potentially limiting the effectiveness of these otherwise potent therapies.”
Cortisol is a hormone naturally produced by the body in response to stress. Chronically elevated cortisol levels, known as Cushing’s syndrome, can lead to a range of problematic symptoms, including metabolic disorders. Cushing’s disease, the most common type of Cushing’s syndrome, is caused by a tumor in the pituitary gland.
“Screening for [high cortisol levels] and considering cortisol-directed treatment is a key part of managing type 2 diabetes in patients not responding to standard-of-care treatments,” said Sloan.
Korlym outperforms placebo in trial
Korlym, which works by blocking receptors that respond to cortisol, is an oral medication approved in the U.S. to help control blood sugar levels in certain people with Cushing’s syndrome who have glucose intolerance or type 2 diabetes.
The Phase 4 CATALYST clinical trial (NCT05772169) measured cortisol in more than 1,000 people with hard-to-control diabetes, with results showing that nearly one in four had abnormally high cortisol levels. Then, more than 100 patients with high cortisol levels were randomly assigned to take Korlym or a placebo for about six months. Results showed Korlym was better than a placebo at reducing blood sugar levels and promoting weight loss.
GLP-1 is a naturally occurring receptor in the body that helps regulate appetite and digestion. Recently, several agonists (activators) of GLP-1 have received approval to treat a range of metabolic disorders. Perhaps the best known is semaglutide (sold as Ozempic, among others). The new analysis covered outcomes from 71 participants in the placebo-controlled treatment portion of CATALYST who were taking GLP-1 agonists or tirzepatide (sold as Mounjaro and Zepbound), which activates GLP-1 and also another receptor called GIP.
Among patients taking GLP-1-targeting therapies, Korlym outperformed a placebo in reducing a measure of blood sugar called HbA1c, with a between-group difference of 1.7%. Korlym also bested placebo at reducing body weight by 6.1 kg (about 13 pounds), and at reducing waist circumference and body mass index (BMI, a ratio of weight to height).
“Data consistently show that [elevated cortisol] is an underlying driver of treatment resistant cardiometabolic disease, including in patients receiving best-in-class therapies like GLP-1s,” said Bill Guyer, Corcept’s chief development officer. “Data from CATALYST demonstrate that treatment with a cortisol modulator, such as Korlym, can be synergistic with GLP-1s or tirzepatide to help patients better control type 2 diabetes. It is our hope that this new research will lead to increased screening for hypercortisolism and improved treatment.”
