Key takeaways:
- Mifepristone decreased HbA1c and weight in sufferers with hypercortisolism and difficult-to-control kind 2 diabetes.
- Screening sufferers with difficult-to-control diabetes for hypercortisolism is a viable technique.
CHICAGO — In sufferers with hypercortisolism and inadequately managed kind 2 diabetes, mifepristone lowered HbA1c ranges by about 1.5% over 24 weeks in contrast with placebo, in keeping with the ultimate outcomes of the CATALYST trial.
As Healio beforehand reported, partially one of many CATALYST trial, researchers decided that the prevalence of hypercortisolism was 24% in a cohort of sufferers with an HbA1c of seven.5% to 11.5% regardless of being on a number of medicines. For half two, the researchers enrolled 136 sufferers with hypercortisolism from half 1 who underwent random project to mifepristone (Korlym, Corcept Therapeutics), a glucocorticoid receptor antagonist, or placebo. The ultimate outcomes of half two had been offered on the American Diabetes Affiliation Scientific Periods and concurrently revealed in Diabetes Care.
The invention that so many sufferers partially one had hypercortisolism “was extraordinarily thrilling, as a result of to my information, there has by no means been something that we thought would possibly account for twenty-four% of individuals which might be difficult to handle in diabetes care,” John B. Buse, MD, PhD, the Verne S. Caviness Distinguished Professor of Medication and director of the UNC Diabetes Middle at College of North Carolina College of Medication, advised Healio. “What was unknown was whether or not we might do something about it. So half two concerned taking these folks with difficult-to-control kind 2 diabetes who had proof of hypercortisolism, doing a little further screening to find out the reason for hypercortisolism, after which randomizing them to mifepristone or placebo to see if the drug would enhance their glycemic management.”
The cohort had a imply age of 63.2 years, 61% had been males and imply baseline HbA1c was 8.55%. All had been on a number of glucose-lowering medicines; some had been on a number of blood strain medicines and in addition had proof of a microvascular or macrovascular complication at baseline.
Enhancements at 24 weeks
At 24 weeks, HbA1c declined from 8.62% to 7.12% within the mifepristone group (least squares imply change, –1.47 share factors; 95% CI, –1.79 to –1.14) in contrast with a decline from 8.41% to eight.36% within the placebo group (least squares imply change, –0.15 share factors; 95% CI, –0.56 to 0.27). The imply distinction in HbA1c between the teams was –1.32 share factors (95% CI, –1.81 to –0.83; P < .001), in keeping with the researchers.
The distinction in HbA1c discount occurred although individuals within the mifepristone group “decreased a number of of their antidiabetes medicines,” Buse advised Healio. “In some methods, a 1.5 [percentage point] discount in HbA1c is an underestimate of what the potential impact actually is.”
In contrast with the placebo group, the mifepristone group at 24 weeks additionally had reductions in physique weight (– 4.4 kg; 95% CI, –6.275 to –2.525 vs. achieve of 0.72 kg; 95% CI, –1.838 to three.272; placebo-adjusted least squares imply change, –5.12 kg; 95% CI, –8.203 to –2.031), BMI (–1.47 kg/m2; 95% CI, –2.096 to –0.841 vs. achieve of 0.28 kg/m2; 95% CI, –0.577 to 1.131; placebo-adjusted least squares imply change, –1.75 kg/m2; 95% CI, –2.799 to –0.713) and waist circumference (–5.2 cm; 95% CI, –7.25 to –3.21 vs. –0.1 cm; 95% CI, –2.74 to 2.51; placebo-adjusted least squares imply change, –5.1 cm; 95% CI, –8.23 to –1.99), in keeping with the researchers.
Security of mifepristone
Mifepristone was related to a rise in blood strain. At 24 weeks, systolic BP rose 8 mm Hg within the mifepristone group (95% CI, 3.82-12.18) in contrast with a drop of –2.1 mm Hg within the placebo group (95% CI, –7.47 to three.27; placebo-adjusted least squares imply change, 10.1 mm Hg; 95% CI, 3.62-16.59), the researchers discovered.
The speed of remedy discontinuation was 46% within the mifepristone group in contrast with 18% within the placebo group.
Buse stated the protection profile was in line with what’s already identified about mifepristone. Hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea and dizziness every occurred in no less than 10% of individuals within the mifepristone group.
“This drug requires consideration to potassium and medical symptom, however nothing new or stunning got here up,” he stated.
The outcomes recommend that “we must be screening for hypercortisolism with the 1 mg in a single day dexamethasone suppression check in a big proportion of our sufferers with kind 2 diabetes, particularly, people who appear to have multimorbidity illness and are on a number of medicine,” Buse advised Healio. “Extra sufferers that screened constructive in our research had heart problems, in addition to despair or different neuropsychiatric circumstances. Extra sufferers had ache and had been taking analgesics. They weren’t doing effectively of their diabetes management. If hypercortisolism is recognized … remedy directed at cortisol can dramatically enhance not solely glycemic management however weight. We felt it was very possible that mifepristone created these enhancements within the setting of hypercortisolism. However what this actually proves is that that utilizing the DST as an preliminary screening technique is ample. That’s in all probability a very powerful level for the endocrine group.”
Reference:
For extra data:
John B. Buse, MD, PhD, will be reached at jbuse@med.unc.edu.
Sources/Disclosures
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Buse JB, et al. Symposium – Remedy of hypercortisolism in folks with difficult-to-control kind 2 diabetes — Ultimate outcomes of the CATALYST trial. Introduced at: American Diabetes Affiliation Scientific Periods; June 20-23, 2025; Chicago.
Disclosures:
The CATALYST research was funded by Corcept Therapeutics. Buse experiences consulting or serving on an advisory panel for Altimmune, Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, Embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Well being, Metsera, Novo Nordisk, Pendulum Therapeutics, Pratego, Stability Well being, Tandem Diabetes Care, Terns, Vertex and Zealand; receiving analysis assist from Corcept Therapeutics, Dexcom and Novo Nordisk; and holding fairness in Glyscend, Mellitus Well being, Metsera, Pendulum Therapeutics, Pratego and Stability Well being. Please see the research for all different authors’ related monetary disclosures.
