Hypercortisolism is common and treatable in difficult-to-treat diabetes, analyses show
Presenters: Lance Sloan, MD, Texas Institute for Kidney and Endocrine Disorders, Lufkin, TX
Effects of mifepristone in people with difficult-to-control T2D and hypercortisolism on GLP-1RAs. Presented June 6, 2026.
Guillermo Umpierrez, MD, Emory University School of Medicine, Atlanta, GA
High prevalence of endogenous hypercortisolism in patients with type 2 diabetes and resistant hypertension: results from the MOMENTUM study. Presented June 7, 2026.
Excess cortisol is a treatable driver of type 2 diabetes that frequently goes undetected in patients with difficult-to-control type 2 diabetes or resistant hypertension, according to analyses presented at the American Diabetes Association (ADA) 2026 Scientific Sessions.
One analysis, from the CATALYST trial, found that the cortisol-blocking drug mifepristone lowered hemoglobin A1c, body weight, and waist circumference in patients with difficult-to-control type 2 diabetes and hypercortisolism, including those already taking a glucagon-like peptide 1 (GLP-1) receptor agonist or the GLP-1/glucose-dependent insulinotropic polypeptide (GIP) dual agonist tirzepatide.
A second study, MOMENTUM, found that more than one in four patients with resistant hypertension had unrecognized hypercortisolism, a share that climbed higher among those with elevated hemoglobin A1c.
Together, the analyses make the case that patients whose disease fails to respond to standard therapy should be screened for excess cortisol, the authors reported.
Hypercortisolism, also known as Cushing syndrome, may blunt the effect of GLP-1 receptor agonists or tirzepatide by disrupting the incretin system, impairing beta-cell function, and inducing insulin resistance, according to the CATALYST investigators.
“Screening for hypercortisolism and considering cortisol-directed treatment is a key part of managing type 2 diabetes in patients not responding to standard-of-care treatments,” investigator Lance Sloan, MD, said in a statement.
Hypercortisolism, caused by excess activity of the hormone cortisol, can produce hypertension, central obesity, and elevated blood sugar, and is more common than previously recognized, recent research has shown.
CATALYST: Cortisol blockade on top of GLP-1 therapy
CATALYST screened 1,057 patients with difficult-to-control type 2 diabetes, defined as a hemoglobin A1c level of 7.5% to 11.5% despite multiple glucose-lowering medications, and found hypercortisolism in 24% of them, according to reported data.
Hypercortisolism was defined as a cortisol level above 1.8 µg/dL on a 1-mg dexamethasone suppression test, the authors noted in their report.
In the treatment phase, 136 patients with hypercortisolism were randomized in a 2:1 ratio to receive mifepristone 300 to 900 mg once daily or placebo for 24 weeks.
The analysis presented at ADA focused on the participants who were taking a GLP-1 receptor agonist or tirzepatide before the study and for at least 80% of it, who numbered 71 patients. In that subgroup, mifepristone reduced hemoglobin A1c by 1.7 percentage points, body weight by 6.1 kg, and waist circumference by 6.5 cm relative to placebo, the largest improvements seen across the trial's groups (all P < .05), the authors reported.
In the overall treatment population, mifepristone lowered hemoglobin A1c by 1.3 percentage points (P < .001), body weight by 5.1 kg, and waist circumference by 5.1 cm versus placebo.
The most common adverse events, each affecting more than 10% of patients, were hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, according to the reported data.
“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,” Dr. Sloan said.
MOMENTUM: How often cortisol excess hides in resistant hypertension
MOMENTUM was a cross-sectional study that screened 1,086 adults with resistant hypertension, defined by American Heart Association criteria, using the same 1-mg dexamethasone suppression test, according to the authors.
Hypercortisolism was present in 27.3% of participants overall, and in 32.6% of those with an hemoglobin A1c of 7.5% or higher, the authors reported.
That pattern paralleled the one in CATALYST, in which 36.6% of patients with type 2 diabetes and a hemoglobin A1c of 7.5% or higher who were taking at least three antihypertensives had hypercortisolism, the authors noted.
Among patients with elevated hemoglobin A1c, those with hypercortisolism also carried a higher burden of diabetes medications and atrial fibrillation than those without it.
Both studies support routine screening for hypercortisolism in patients whose diabetes or hypertension resists standard treatment, the authors concluded.
Disclosures
Dr. Sloan reported advisory panel and speaker relationships with Corcept Therapeutics and several other companies. Several co-authors reported research support or consulting arrangements with Corcept, and Austin L. Hand, Tina K. Schlafly, and Daniel F. Einhorn are Corcept employees. Both CATALYST and MOMENTUM were sponsored by Corcept Therapeutics.
References
Sloan L, Aroda V, Busch RS, et al. Effects of mifepristone in people with difficult-to-control T2D and hypercortisolism on GLP-1RAs. Abstract 1219-OR. Presented at American Diabetes Association 86th Scientific Sessions; June 6, 2026; New Orleans, LA.
Umpierrez G, Aroda V, Budoff M, et al. High prevalence of endogenous hypercortisolism in patients with type 2 diabetes and resistant hypertension: results from the MOMENTUM study. Abstract 2970-LB. Presented at American Diabetes Association 86th Scientific Sessions, June 2026, New Orleans, LA.
Corcept Therapeutics. Corcept presents new data at ADA: improved outcomes in patients receiving a GLP-1 with difficult-to-control type 2 diabetes and hypercortisolism treated with Korlym (news release). June 6, 2026. https://www.businesswire.com/news/home/20260606758364/en