Mifepristone reduces HbA1c in patients with hypercortisolism, type 2 diabetes
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Key takeaways:
- Mifepristone reduced HbA1c at 24 weeks vs. placebo in patients with hypercortisolism and hard-to-control type 2 diabetes.
- Almost one-fourth of a cohort with hard-to-control type 2 diabetes had hypercortisolism.
In patients with hypercortisolism and difficult-to-control type 2 diabetes, mifepristone lowered HbA1c at 24 weeks compared with placebo, researchers reported at World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
“I think [these results are] going to change how we manage these challenging patients,” Vivian A. Fonseca, MD, FRCP, professor of medicine, assistant dean for clinical research, the Tullis-Tulane Alumni Chair in Diabetes and chief of the section of endocrinology at Tulane University Medical Center, said during a presentation.
Fonseca presented topline results of part two of the CATALYST study, in which patients with hypercortisolism (Cushing’s syndrome) and difficult-to-control type 2 diabetes were randomly assigned to receive mifepristone (Korlym, Corcept Therapeutics) or placebo, and summarized part one of CATALYST, in which researchers determined the prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes and identified predictors of hypercortisolism in this population. The full results of part two of CATALYST will be presented at a medical conference in 2025, according to a press release from Corcept.
For part one, the researchers analyzed 1,057 patients with difficult-to-control type 2 diabetes (mean age, 60.7 years; 45.3% women) and determined that 252 (23.8%; 95% CI, 21.3-26.5) had hypercortisolism, Fonseca said during the presentation.
He said that in a univariate analysis, odds of having hypercortisolism were elevated in the following patients:
- those taking at least two glucose-lowering and at least two blood pressure-lowering medications;
- those taking at least two glucose-lowering medications with at least one micro- or macrovascular complication;
- those taking at least three glucose-lowering medications;
- those taking an SGLT2 inhibitor, with or without insulin;
- those taking a maximum dose of a GLP-1 receptor agonist;
- those taking tirzepatide (Mounjaro, Eli Lilly);
- those taking an SGLT2 inhibitor and a GLP-1 receptor agonist, with or without insulin;
- those taking at least three BP-lowering medications;
- those taking beta-blockers;
- those taking diuretics;
- those taking calcium channel blockers;
- those taking lipid-lowering therapies;
- those taking psychiatric medications;
- those taking analgesics; and
- those taking other cardiovascular medications.
In a multivariate analysis, the following were predictors of hypercortisolism: older age, BMI less than 30 kg/m2, non-Hispanic/Latino ethnicity, taking an SGLT2 inhibitor, taking a maximum dose of a GLP-1 receptor agonist, taking tirzepatide, taking BP medications from multiple classes, taking fibrates and taking analgesics, Fonseca said.
“Some of the newer medications that have worked very well for a lot of our patients don’t work in some people,” Fonseca said during the presentation.
The prevalence of hypercortisolism was 36.6% in patients taking at least three BP medications, he said.
Compared with those without them, patients with any cardiac disease, coronary artery disease, atrial fibrillation and congestive heart failure were more likely to have hypercortisolism, he said.
Among those with hypercortisolism, approximately one-third had an adrenal abnormality confirmed by an abdominal CT scan, he said.
The patients from part one of CATALYST diagnosed with hypercortisolism were invited to enroll in part two, and 136 of them did, according to the release. Mean HbA1c at baseline was 8.6% in the mifepristone group and 8.4% in the placebo group.
At 24 weeks, those assigned mifepristone had a least-squares mean change in HbA1c from baseline of –1.47% (P < .0001), compared with –0.15% for those assigned placebo (P = .92; between-group difference, –1.32 percentage points; P < .0001), Fonseca said during the presentation.
The safety profile of mifepristone was consistent with its labeling and no new adverse events emerged, he said.
“I think this is going to change how we approach people that we in the past thought were very difficult to control ... to a more precise therapy based on an abnormality that will lead to success,” Fonseca said.
Reference:
Corcept announces positive results in treatment phase of CATALYST trial in patients with hypercortisolism (Cushing’s syndrome) and difficult-to-control diabetes. Available at: https://ir.corcept.com/news-releases/news-release-details/corcept-announces-positive-results-treatment-phase-catalyst. Published Dec. 12, 2024.
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Fonseca VA, et al. Session 16: Emerging topics in cardiometabolic diseases. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 12-14, 2024; Los Angeles.
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