Korlym lowers blood sugar, weight in people with Cushing’s, diabetes
Study: Patients also had a smaller waistline, reduced or stopped medications
Korlym (mifepristone) lowered the levels of hemoglobin A1c (HbA1c), which reflects the average amount of blood sugar over the past three months, in people with Cushing’s syndrome and treatment-resistant type 2 diabetes.
That’s according to newly published data from the now-complete Phase 4 CATALYST (NCT05772169) clinical trial, which also showed Korlym-treated patients lost weight, had a smaller waistline, and reduced or stopped medications that lower blood sugar.
“The CATALYST results will help physicians more accurately diagnose and treat people with [Cushing’s syndrome], a serious and deadly disease that too often goes undetected,” Bill Guyer, chief development officer of Corcept Therapeutics, the therapy’s marketer, said in a company press release.
CATALYST data were described in the study, “Inadequately Controlled Type 2 Diabetes and Hypercortisolism: Improved Glycemia With Mifepristone Treatment,” which was published in Diabetes Care and presented at the American Diabetes Association’s 85th Scientific Sessions, held recently in Chicago.
Patients spend years seeking symptom’s causes
Cushing’s syndrome is a group of conditions marked by high blood levels of the hormone cortisol, also called hypercortisolism. One of its most common forms, Cushing’s disease, is caused by a tumor in the brain’s pituitary gland. These tumors secrete large amounts of adrenocorticotropic hormone, a signaling molecule that stimulates cortisol production.
Among its many functions in the body, cortisol helps to regulate blood sugar or glucose levels. Too much of the hormone boosts blood sugar levels, which may lead to glucose intolerance and type 2 diabetes.
“We urgently need all physicians, not just endocrinologists, to develop a greater understanding of Cushing’s syndrome,” said Leslie Edwin, a Cushing’s patient and president of the Cushing’s Support & Research Foundation. “Patients are still spending years on average searching for the cause of deceptively common symptoms, like elevated blood sugar, weight gain, depression and anxiety treated as individual diagnoses instead of parts of a bigger, more burdensome problem that carries tremendous health risk.”
Korlym significantly outperformed placebo in reducing hemoglobin A1c
Korlym is an oral therapy designed to block cortisol receptors, thereby preventing blood sugar levels from rising. It’s approved to control blood sugar in adults with Cushing’s syndrome with glucose intolerance or type 2 diabetes, as well as in cases where surgery is ineffective or not an option.
CATALYST was a two-part study that enrolled patients at 36 sites across the U.S. In the first part, the researchers screened for hypercortisolism in 1,057 people with hard-to-treat type 2 diabetes — defined as HbA1c greater than 7.5% despite receiving multiple glucose-lowering medications. Overall, 23.8% had hypercortisolism.
“Many people with type 2 diabetes do not respond adequately to conventional glucose-lowering therapies,” said John Buse, MD, PhD, director of the University of North Carolina’s Diabetes Center.
In the second part of CATALYST, 136 patients who completed the first part and had hemoglobin A1c levels between 7.5% and 11.5% were randomly assigned to receive once-daily Korlym (300mg to 900 mg) or a placebo for about six months.
Data reported late last year showed Korlym outperformed the placebo in significantly reducing hemoglobin A1c from the study’s start (1.47% vs. 0.15%), meeting the trial’s primary objective.
Treatment with a cortisol-directed therapy can confer significant clinical benefits, including meaningful reductions in HbA1c, body weight, and waist circumference.
Newly presented data showed patients who received the 900 mg dose had the largest reduction in hemoglobin A1c over the placebo (2.01% vs. 0.16%).
In secondary measures, Korlym-treated patients lost a mean of 5.1 kg (11.2 lbs) more weight and had a smaller waist circumference by a mean of 5.1 cm (2 inches) than those who received a placebo. These improvements were seen despite patients reducing or discontinuing their glucose-lowering medications.
“Treatment with a cortisol-directed therapy can confer significant clinical benefits, including meaningful reductions in HbA1c, body weight, and waist circumference,” Buse said. “These powerful findings provide important guidance for physicians treating patients with difficult-to-control type 2 diabetes.”
More participants treated with Korlym discontinued treatment than those on a placebo (46% vs. 18%). Adverse events that occurred in more than 10% of patients included low potassium (hypokalemia), fatigue, nausea, vomiting, headache, peripheral swelling (edema), diarrhea, and dizziness. These side effects were consistent with Korlym’s safety profile, the researchers noted. Blood pressure increases also occurred.
“One in four patients with difficult-to-control type 2 diabetes have hypercortisolism and treatment with a cortisol modulator can be highly effective in improving many of their signs and symptoms,” Guyer said. “Corcept is thankful to the patients who participated in CATALYST. We hope these data can help all patients with this disease.”
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