Adrenalectomy versus semaglutide for metabolic health in mild autonomous cortisol secretion
Official title: IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion
Run by University of Texas Southwestern Medical Center · NCT07361874 · Data updated 2026-11-12
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
| Study type | Interventional |
|---|---|
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 75 (estimated) |
| Sponsor | University of Texas Southwestern Medical Center Academic / other |
| Locations | 1 site (Dallas, Texas) |
| Status | Recruiting |
| Started | March 5, 2026 |
| Main results expected | May 31, 2030 |
| Study ends | May 31, 2030 |
| Registry record updated | March 27, 2026 |
| Trial ID | NCT07361874 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a 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.
✕Probably 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.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
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.
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 gone: 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.
Who can join: the full rules
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 it's running
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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
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Metyrapone for Mild Autonomous Cortisol Secretion
This study tests whether taking metyrapone by mouth for six months can safely reduce cortisol excess in adults with MACS compared with a placebo.
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Adrenal Diseases in Modena: A Patient Registry at Modena University Hospital
This study collects medical histories and treatment data from patients with adrenal diseases to see how they are diagnosed and managed in Modena.
-
Tirzepatide after adrenalectomy for MACS
This study tests whether adding tirzepatide after adrenalectomy helps control blood pressure and improve metabolic health in adults with mild autonomous cortisol secretion.
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Metyrapone versus osilodrostat for metabolic autonomous cortisol secretion (MACS)
This trial will test whether metyrapone or osilodrostat better lowers cortisol and improves health in adults with mild autonomous cortisol secretion (MACS) who are not having surgery.
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Isturisa treatment for people with mild autonomous cortisol secretion (MACS)
This trial will test whether Isturisa (osilodrostat) helps adults with MACS improve metabolic measures, blood pressure, weight, bone density, and quality of life.
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Low-dose (1 mg) osilodrostat for mild autonomous cortisol secretion
This trial will test whether taking 1 mg of osilodrostat daily is safe and can lower cortisol measures in adults with mild autonomous cortisol secretion.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.