IMPACT-MACS

RecruitingPhase NA

IMPACT-MACS: Adrenalectomy vs Semaglutide for Metabolic Outcomes in Mild Autonomous Cortisol Secretion

IMPACT-MACS Study: Investigating the Mechanisms, Pathophysiology, and Cardiometabolic Treatment in Mild Autonomous Cortisol Secretion

Lead sponsor

University of Texas Southwestern Medical Center

Assets

GLP-1 / incretin class catch-all / Semaglutide

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Obesity / overweight

Key I/E criterion

•BMI ≥27

Primary endpoint

•Insulin Sensitivity (M-value), mg/kg/min

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07361874

Org study IDSTU20251717

Secondary ID1K23DK142038-01A1

Timeline

Milestones

Study first posted2026-01-23actual

Study start2026-03-05actual

Last update posted2026-03-27actual

Primary completion2030-05-31estimated

Study completion2030-05-31estimated

Assets

Investigational agents

GLP-1 / incretin class catch-all Semaglutide

Study populations

Who this study enrolls

Obesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (37)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Cardiometabolic biomarkers

Other clinical outcomes

Weight & body composition

Glycemic / diabetes

Patient-reported / QoL

Safety / tolerability / PK

Weight & body composition

5 endpoints

Secondary/protocol endpoint

Change in body weight, kg

Time frame:Baseline to Week 26

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in BMI, kg/m2

Time frame:Baseline to Week 26

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in waist circumference, cm

Time frame:Baseline to Week 26

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Change in fat area, cm2

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in muscle area, cm2

Time frame:Baseline to Week 26

change from baseline, improvement

Glycemic / diabetes

5 endpoints

Primary/protocol endpoint

Change in Insulin Sensitivity (M-value), mg/kg/min

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in fasting plasma glucose, mg/dL

Time frame:Baseline to Week 26

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in hemoglobin A1C, %

Time frame:Baseline to Week 26

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in fasting insulin, µU/mL

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in c-peptide, nmol/L

Time frame:Baseline to Week 26

C-peptide AUC

change from baseline, improvement

Cardiometabolic biomarkers

7 endpoints

Secondary/protocol endpoint

Change in leptin, ng/mL

Time frame:Baseline to Week 26

Leptin, change

change from baseline, improvement

Secondary/protocol endpoint

Change in adiponectin, μg/mL

Time frame:Baseline to Week 26

Adiponectin, change

change from baseline, improvement

Secondary/protocol endpoint

Mean change in systolic BP, mmHg

Time frame:Baseline to Week 26

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Mean change in diastolic BP, mmHg

Time frame:Baseline to Week 26

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Change in cholesterol, mg/dL

Time frame:Baseline to Week 26

Total cholesterol, change

change from baseline, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in Free Fatty Acids, mmol/L

Time frame:Baseline to Week 26Baseline to Week 26

Free fatty acids, change

change from baseline, improvement

Secondary/protocol endpoint

Change in C-reactive protein, pg/mL

Time frame:Baseline to Week 26

change from baseline, improvement

Patient-reported / QoL

5 endpoints

Secondary/protocol endpoint

Change in overall quality of life, score

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in disease-specific QoL, score

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in mood, score

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in sleep, score

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in eating behavior, score

Time frame:Baseline to Week 26

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Adverse Events and Serious Adverse Events

Time frame:Baseline through Week 30

Serious AEs (any)

descriptive

Other clinical outcomes

6 endpoints

Secondary/protocol endpoint

% of patients with normal dexamethasone suppression test, %

Time frame:Baseline to Week 26

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Change in bone mineral density, mg/cm³

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in chair rise test, stands/30s

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in Hand Grip Strength, kg

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in cognition, seconds

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint

Change in frailty, score

Time frame:Baseline to Week 26

change from baseline, improvement

Other (unclassified)

8 endpoints

Secondary/protocol endpoint/low confidence

Change in glucagon, pg/mL

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in IGF-1, ng/mL

Time frame:Baseline to Week 26

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in IGF-II, ng/mL

Time frame:Baseline to Week 26

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in IGFBP-1, ng/mL

Time frame:Baseline to Week 26

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in steroid profile, ng/24h

Time frame:Baseline to Week 26

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in TNF-alpha, pg/mL

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in Interleukin-1, pg/mL

Time frame:Baseline to Week 26

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in Interleukin-6, pg/mL

Time frame:Baseline to Week 26

change from baseline, improvement

Publications (8)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.
European journal of endocrinology2023 Jul 20PMID37318239doi:10.1093/ejendo/lvad066via CT.gov background
Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.
Annals of internal medicine2022 Mar (month)PMID34978855doi:10.7326/M21-1737via CT.gov background
Approach to the Patient With Adrenal Incidentaloma.
The Journal of clinical endocrinology and metabolism2021 Oct 21PMID34260734doi:10.1210/clinem/dgab512via CT.gov background
Assessment of mild autonomous cortisol secretion among incidentally discovered adrenal masses.
Best practice & research. Clinical endocrinology & metabolism2021 Jan (month)PMID33593680doi:10.1016/j.beem.2021.101491via CT.gov background
Epidemiology of adrenal tumours in Olmsted County, Minnesota, USA: a population-based cohort study.
The lancet. Diabetes & endocrinology2020 Nov (month)PMID33065059doi:10.1016/S2213-8587(20)30314-4via CT.gov background
Adrenal Incidentalomas are Tied to Increased Risk of Diabetes: Findings from a Prospective Study.
The Journal of clinical endocrinology and metabolism2020 Apr 1PMID31900474doi:10.1210/clinem/dgz284via CT.gov background
High prevalence of obesity in patients with non-functioning adrenal incidentalomas.
Neuro endocrinology letters2010 (year)PMID20588242via CT.gov background
Prevalence of adrenal incidentaloma in a contemporary computerized tomography series.
Journal of endocrinological investigation2006 Apr (month)PMID16699294doi:10.1007/BF03344099via CT.gov background

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.