Adrenalectomy versus semaglutide for metabolic health in mild autonomous cortisol secretion
IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion
NA · University of Texas Southwestern Medical Center · NCT07361874
We are testing whether removing the adrenal gland or treating with semaglutide better improves insulin resistance and other metabolic measures in adults with mild autonomous cortisol secretion, and comparing semaglutide effects to matched adults without adrenal tumors.
Quick facts
| Phase | NA |
|---|---|
| Study type | Interventional |
| Enrollment | 75 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Texas Southwestern Medical Center (other) |
| Locations | 1 site (Dallas, Texas) |
| Trial ID | NCT07361874 on ClinicalTrials.gov |
What this trial studies
This single-center, prospective interventional trial randomizes adults with MACS to either adrenalectomy or semaglutide and includes a parallel matched control arm in which controls without adrenal tumors receive semaglutide. The primary outcome is change in insulin sensitivity measured by hyperinsulinemic-euglycemic clamp (M-value) from baseline to week 26. Secondary outcomes include cortisol dynamics and steroid profiling, cardiometabolic biomarkers, body composition, blood pressure, muscle strength, and patient-reported quality of life. Semaglutide is given within its FDA-approved indication for weight management and adrenalectomy is delivered as standard clinical care.
Who should consider this trial
Good fit: Ideal candidates are adults with MACS (adrenal adenoma and DST cortisol >1.8 µg/dL) who are eligible for adrenalectomy and willing to delay surgery for six months if randomized, as well as matched control adults without adrenal abnormalities who meet BMI and cardiometabolic criteria.
Not a fit: Patients with overt Cushing's, type 1 diabetes, recent GLP-1 receptor agonist use, contraindications to semaglutide or to postponing surgery, or serious organ dysfunction are excluded and would not be expected to benefit from participation.
Why it matters
Potential benefit: If successful, the trial could identify whether surgery or semaglutide more effectively improves insulin resistance and cardiometabolic risk in people with MACS, guiding treatment decisions.
How similar studies have performed: GLP-1 receptor agonists have established metabolic benefits and adrenalectomy has shown metabolic improvements in retrospective series, but randomized head-to-head comparisons in MACS are novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Adults ≥18 years * MACS groups: adrenal adenoma + DST cortisol \>1.8 µg/dL + no overt Cushing + eligible for adrenalectomy * Willingness to postpone surgery 6 months if randomized * Controls: no adrenal abnormalities + normal DST + BMI ≥27 + ≥2 cardiometabolic conditions * Stable medication doses for ≥4 weeks * Negative pregnancy test if applicable Exclusion Criteria: * Prior GLP-1 RA within 90 days * Weight change \>5 kg in past 90 days * Prior obesity/diabetes surgery * Type 1 diabetes or other diabetes types * Severe organ disease * Recent pancreatitis * Pregnancy, breastfeeding * Contraindication to semaglutide * Contraindication to surgery delay * Chronic glucocorticoid use
Where this trial is running
Dallas, Texas
- University of Texas Southwestern Medical Center — Dallas, Texas, United States (RECRUITING)
Study contacts
- Study coordinator: Oksana Hamidi, DO, MSCS
- Email: oksana.hamidi@utsouthwestern.edu
- Phone: 214-645-6397
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Mild Autonomous Cortisol Secretion, Autonomous Cortisol Secretion, Subclinical Cushing's, Mild Autonomous Cortisol Excess, MACS, Adrenal incidentaloma, Adrenal adenoma, Subclinical Cushing