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

What Was Tested

In this not phased trial, researchers set out to test Semaglutide.

The goal of this study is to learn how two treatments-adrenalectomy (surgical removal of an adrenal gland) and semaglutide (a medication used for weight management)-affect insulin resistance and cortisol regulation in adults with mild autonomous cortisol secretion (MACS).

The study will also learn how these treatments impact body composition, blood pressure, cholesterol, inflammation, muscle strength, and quality of life.

The main questions the study aims to answer are: 1.

It had three arms (groups): Arm 1: Adrenalectomy (MACS) (active comparator), Arm 2: Semaglutide (MACS) (active comparator) and Arm 3: Semaglutide (Matched Controls) (active comparator).

Adults with mild autonomous cortisol secretion (MACS) who are clinically eligible for adrenalectomy undergo unilateral adrenalectomy as part of standard care. Participants complete all metabolic assessments before and after treatment.

The registry classes the interventions as drug and procedure.

More on the Plan

The study includes: 1. a randomized controlled trial comparing adrenalectomy to semaglutide in MACS, and 2. a parallel matched case-control comparison evaluating semaglutide effects in MACS versus matched controls without adrenal tumors.

The primary objective is to compare changes in insulin sensitivity measured by hyperinsulinemic-euglycemic clamp (M-value) from baseline to week 26.

Secondary outcomes include cortisol dynamics, steroid profiling, cardiometabolic biomarkers, body composition, blood pressure, muscle strength, and patient-reported quality of life.

Semaglutide is administered within its FDA-approved indication for weight management; adrenalectomy is standard of care.

Who Took Part

75 planned participants were the target.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Adults ≥18 years. Willingness to postpone surgery 6 months if randomized. Controls: no adrenal abnormalities + normal DST + BMI ≥27 + ≥2 cardiometabolic conditions. Negative pregnancy test if applicable.

The full record lists 6 inclusion and 10 exclusion criteria; among the exclusions: prior glp-1 ra within 90 days; weight change \>5 kg in past 90 days; severe organ disease.

How the Study Was Run

The set-up was randomized, parallel-group and open-label.

The participants were allocated by chance, so the Semaglutide group and the comparison group should start out alike.

The Semaglutide group and the comparison group ran side by side rather than switching.

Nothing was hidden in this open-label Semaglutide study: the participants and staff both knew the treatment.

It started in 2026-03-05 with completion listed for 2030-05-31.

It ran at 1 site in United States.

Its stated primary purpose is treatment.

What Was Measured

It also tracked 36 secondary outcomes, for example Change in fasting plasma glucose, mg/dL, Change in hemoglobin A1C, %, Change in fasting insulin, µU/mL, Change in glucagon, pg/mL, Change in c-peptide, nmol/L and Change in IGF-1, ng/mL.

What This Means in Plain Language

Put simply, this is a not phased, randomized trial of Semaglutide in 75 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Semaglutide compound page, all human trials.