Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion

May 1, 2026 updated by: Alaa Sada

A Randomized Clinical Trial of Tirzepatide Following Adrenalectomy in Mild Autonomous Cortisol Secretion

Mild Autonomous Cortisol Secretion (MACS) is a condition in which an adrenal gland produces excess cortisol and is associated with high blood pressure, diabetes, and weight gain. Surgical removal of the adrenal gland (adrenalectomy) is standard treatment, but some patients continue to have metabolic health problems after surgery.

This randomized study will evaluate whether treatment with tirzepatide after adrenalectomy improves metabolic outcomes in patients with MACS compared with adrenalectomy alone.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This prospective, randomized study will enroll adults with MACS and elevated blood pressure who are undergoing unilateral adrenalectomy. Following surgery, participants will be randomized in a 1:1 ratio to one of two groups: adrenalectomy alone or adrenalectomy followed by tirzepatide therapy for 12 months. Tirzepatide will be prescribed and managed by the study team in accordance with current standard-of-care practices, including routine clinical monitoring and dose adjustments.

The primary focus of the study is to evaluate blood pressure control at 12 months. Secondary outcomes include change in body weight, body mass index, glycemic control, medication burden, and patient-reported quality of life. This study aims to generate preliminary data on the feasibility, safety, and potential additive metabolic benefits of combining pharmacologic incretin-based therapy with surgical management of MACS.

Study Type

Interventional

Enrollment (Estimated)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged 18 years and older
  • Diagnosis of MACS, defined as morning cortisol >1.8 mcg/dL after a 1 mg dexamethasone suppression test
  • Elevated blood pressure (SBP ≥120 mmHg or DBP ≥80 mmHg per the 2017 American College of Cardiology/American Heart Association [ACC/AHA] criteria, or current use of antihypertensive medication)
  • BMI ≥27
  • Undergoing or having undergone adrenalectomy for the treatment of MACS

Exclusion Criteria:

  • Bilateral adrenal lesions
  • Adrenal malignancy
  • Concurrent primary aldosteronism with MACS
  • Current use of GLP-1 receptor agonists
  • Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2)
  • Pregnancy or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: GLP-1 Treatment
GLP-1 dose of 2.5 mg once weekly for 4 weeks. The dose will then be titrated every 4 weeks based on patient tolerance to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.
Drug: Tirzepatide
Tirzepatide will be initiated at the lowest dose of 2.5 mg once weekly for 4 weeks. The dose will then be titrated every 4 weeks based on patient tolerance to 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.
Active Comparator: Standard of Care arm
Participants in this arm will receive standard of care management for as determined by their treating clinician.
Other: Standard medical treatment
Participants will receive postoperative care and follow up per institutional standard-of-care practices

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in systolic blood pressure
Time Frame: Baseline and 12 months
Changes in blood pressure will be assessed based on patients' average blood pressure readings, mmHg
Baseline and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
weight
Time Frame: Baseline and 12 months
Change in participant weight, Kg
Baseline and 12 months
medication
Time Frame: Baseline and 12 months reported in WHO defined daily doses (DDDs)
any change in medication expressed as defined daily doses (DDDs)
Baseline and 12 months reported in WHO defined daily doses (DDDs)
HbA1c
Time Frame: Baseline and 12 months, %
change in HbA1c levels
Baseline and 12 months, %
quality of life metrics
Time Frame: Baseline and 12 months
quality of life metrics will measured using the 36-Item Short Form Health Survey (SF-36) which is a validated measure of health-related quality of life assessing eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain is scored from 0 to 100, with higher scores indicating better health status. Domain scores may be analyzed individually or combined using standard scoring algorithms to generate the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, which are norm-based (mean 50, SD 10); higher values reflect better physical and mental health, respectively.
Baseline and 12 months
BMI
Time Frame: Baseline and 12 months
Any change in BMI in kg/m2
Baseline and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alaa Sada

Investigators

  • Principal Investigator: Alaa Sada, MD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

July 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

May 1, 2026

First Submitted That Met QC Criteria

May 1, 2026

First Posted (Actual)

May 7, 2026

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY25030073

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) will not be publicly shared because the study involves a small sample size from a single center with detailed clinical, laboratory, and imaging data, which may pose a risk of participant re-identification despite de-identification procedures. Aggregate results will be reported in peer-reviewed publications.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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