Osilodrostat improves comorbid hypertension, diabetes for adults with Cushing’s disease
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Key takeaways:
- At 72 weeks, adults with Cushing’s disease and hypertension receiving osilodrostat had reductions in BP.
- Osilodrostat lowered HbA1c from baseline to 72 weeks for those with Cushing’s disease and diabetes.
BOSTON — Long-term osilodrostat therapy may improve symptoms of comorbid cardiometabolic disorders such as hypertension and diabetes for adults with Cushing’s disease, according to data presented at ENDO 2024.
As Healio previously reported, the FDA approved oral osilodrostat (Isturisa, Recordati) in March 2020 for adults with Cushing’s disease who cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. New data from a pooled analysis of two phase 3 trials was conducted to assess the impact of the medication on adults with Cushing’s disease and other comorbid conditions. Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Oregon Health and Science University Pituitary Center and a Healio | Endocrine Today Co-editor, said the analysis was important because people with Cushing’s disease have an increased risk for morbidity and mortality with comorbid cardiometabolic diseases.
“Before initiation of osilodrostat, 83% of patients had hypertension,” Fleseriu told Healio. “The severity of hypertension decreased over long-term osilodrostat treatment. Many patients with hypertension showed improvements in blood pressure, which were maintained or further improved during long-term treatment. ... Before initiation of osilodrostat, 40% of patients had diabetes. The severity of diabetes decreased over long-term osilodrostat treatment. Many patients with diabetes had improved glycemic control, and these improvements were maintained or further improved long term.”
Researchers collected data from 210 adults with Cushing’s disease who participated in the LINC 3 and LINC 4 phase 3 trials. Data were collected at baseline and at weeks 12, 48 and 72, except for periods where participants were receiving placebo. Adults were defined as having hypertension at baseline if they had a prior diagnosis, were taking antihypertensive medication or had a systolic BP of more than 130 mm Hg and a diastolic BP of more than 90 mm Hg. Adults had baseline diabetes if they had a prior diagnosis, were taking diabetes medication or had an HbA1c of 6.5% or higher or a fasting plasma glucose of 126 mg/dL or higher.
Hypertension benefits
Of the study group, 83% had hypertension at baseline and 54% of participants were taking an antihypertensive medication. Reductions in both systolic and diastolic BP were observed from baseline to 72 weeks for participants receiving osilodrostat, regardless of whether they were taking an antihypertensive medication. Adults who achieved complete or partial control of urinary free cortisol levels at 72 weeks had larger reductions in BP than adults who achieved partial control or had uncontrolled levels.
Of 110 adults who had a systolic BP of more than 130 mm Hg at baseline, 49.1% lowered their BP to 130 mm Hg or less at 72 weeks. Of 65 adults with a diastolic BP of more than 90 mm Hg at baseline, 58.5% had a diastolic BP of 90 mm Hg or less at 72 weeks.
“There were also reductions in mean weight, waist circumference and BMI during the studies in patients with and without hypertension at baseline,” Fleseriu said.
Diabetes benefits
At baseline, 40% of adults had diabetes and 22% were using a diabetes medication. Of adults with an FPG of 100 mg/dL or higher at baseline, 33.3% had an FPG of less than 100 mg/dL at 72 weeks. Among adults with an HbA1c of 6.5% or higher at baseline, 62% achieved an HbA1c of less than 6.5% at 72 weeks.
“Similar to hypertension, patients with higher baseline fasting plasma glucose and HbA1c experienced the greatest reductions in these parameters,” Fleseriu said.
Some adults were able to lower their antihypertensive or diabetes medication dose at 72 weeks of osilodrostat therapy. Among those using an antihypertensive medication, 26.8% reduced their dose at 72 weeks, 47.9% had no change in dose and 25.4% increased their dose. For adults using a diabetes medication, 35.7% were receiving a lower dose at 72 weeks of osilodrostat treatment, 53.6% had no change in dose and 10.7% had an increase in diabetes medication dose.
“This study highlights the need to adjust medications for comorbidities such as hypertension and diabetes after treatment for Cushing’s disease as improvement in expected in most, but not all patients,” Fleseriu said.
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Fleseriu M, et al. SUN-059. Presented at: ENDO annual meeting; June 1-4, 2024; Boston.
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