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RecruitingPhase 2

Tirzepatide in MetALD

A Randomized, Double-Blind, Placebo-Controlled, Flexible Dose Phase 2 Study of Efficacy and Safety of Tirzepatide in Individuals With Alcohol Use Disorder and Metabolic Alcohol-associated Liver Disease

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

1

Recruiting sites

1

Enrollment

120

estimated

Study population

Alcohol / substance use, MASH / NAFLD / liver fibrosis, Obesity / overweight

Key I/E criteria

BMI 25-40HbA1c ≥5.7%

Primary endpoint

Metabolic improvement from baseline (Body weight, % change, liver steatosis cap pct change)

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 IDNCT07046819
Org study ID10002246
Secondary ID002246-AA

Timeline

Milestones

Study first posted2025-07-02actual
Study start2026-04-01actual
Last update posted2026-04-03actual
Primary completion2026-07-30estimated
Study completion2026-07-30estimated

Assets

Investigational agents

Study populations

Who this study enrolls

Alcohol / substance useMASH / NAFLD / liver fibrosisObesity / overweight

Eligibility

Who can enroll

Minimum age21 Years
Maximum age100 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

INCLUSION CRITERIA

To be eligible to participate in this study, an individual must meet all of the following criteria:

1. Age 21 or older

2. Ability to provide written informed consent

3. Females: Negative urine pregnancy test, not currently breastfeeding, agree to abstain or use accepted form of contraception including use of oral contraceptives and an additional barrier method of contraceptive such as condoms; use of an approved IUD or other longacting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner(s)

4. Males: Agree to abstain or use accepted form of contraception, such as condoms.

5. Diagnosis of AUD as confirmed by MINI

6. Current alcohol use as assessed via the TLFB (>14 standard drinks per week for males and >7 standard drinks per week for females on average for the last 8 weeks)

7. Liver steatosis as determined by Fibroscan (CAP score >240) at screening

8. BMI >= 25 and <40 kg/m^2

9. metALD as defined by at least one out of 5 criteria at screening:

1. BMI >= 25 and <40 kg/m^2

2. Fasting serum glucose >= 5.6mmol/L [100mg/dL] or HbA1c >=5.7%

3. Blood pressure >=130/85 or specific antihypertensive drug treatment

4. Plasma triglycerides >=1.70mmol/L [150mg/dL] or lipid lowering treatment

5. Plasma HDL-cholesterol less than 1.0mmol/L [40mg/dL] or lipid lowering treatment

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Treatment seeking for alcohol use disorder

2. History of a serious hypersensitivity reaction to GLP-1RA/GIPRA

3. Current/past use of GLP-1RA/GIPRA within the last 3 months

4. Clinically significant and/or unstable cardiovascular disease over the past 12 months

5. History of diabetes mellitus or blood hemoglobin A1c (HbA1c) >= 6.5 % at screening

6. Any underlying clinically significant and/or unstable acute or chronic liver disease unrelated to alcohol use at screening, history of cirrhosis, esophageal varices

7. Subjects with platelets count of less than 110,000/ mm^3

8. Alanine aminotransferase or aspartate aminotransferase exceeding 5 times the upper limit of normal levels at screening

9. Bilirubin 2x UNL or Creatinine > 2 mg/dL at screening

10. Patients with coagulopathy defined as INR >1.5, prothrombin time prolonged by > 3s, and/or platelets <75,000 / mm^3 at screening

11. Positive HIV test or positive Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at screening

12. Chronic renal failure as estimated by glomerular filtration rate (GFR) < 60mL/min/1.73 m^2 at screening

13. History of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

14. History of previous bariatric surgery or transplant surgery

15. Patients with significant hematologic abnormalities, as defined by hemoglobin < 8g/dL and/or white blood count <1500 cells/microL

16. Current or prior history of any clinically significant disease, including, seizure disorder, epilepsy, alcohol related seizures within 12 months of screening, uncontrolled endocrine disease, hemorrhagic stroke, cancer within the past 5 years or any other significant abnormality identified at the time of screening that, in the judgment of the investigator or study clinician, would preclude safe completion of the study

17. Use of any medications that interfere with tirzepatide

18. Use of the following medications with glucose lowering properties in the last 30 days: GLP-1RA, GLP-1RA/GIPRA, insulin, metformin, sulfonylurea, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors

19. Use of the following medications: Any medication that requires intramuscular administration injections. Systemic corticosteroids

20. Use of any investigational drugs within 1 month, or five half-lives, whichever is longer, of the study procedures

21. Presence of any current suicidality or a lifetime history of suicide attempt or suicidal ideation within the past year

22. History of serious mental illnesses including psychotic disorders, bipolar disorders, severe anxiety, mood, or trauma-related disorders and other psychiatric conditions which in the opinion of the investigators would impede the patient's participation or compliance in the study

23. History of liver decompensation events such as hepatic encephalopathy or ascites

24. History of severe gastroparesis

25. History of pancreatitis in the last 5 years or if subject has chronic pancreatitis

For optional MRI:

a)Presence of ferromagnetic objects in the body that may be adversely affected by or contraindicated for MRI, fear of enclosed spaces, or other standard contraindication to MRI, as determined by self-report
b)Use of MRI- incompatible intrauterine device (IUD).

Individuals who are pregnant or breastfeeding, or with severe hepatic or renal liver impairment will be excluded from this study because there is no clinical data on the safety of tirzepatide in these populations, including the impact on the fetus or infant. To assess pregnancy status, participants who can become pregnant will be required to take a urine pregnancy test and to test negative before administering study drug.

Endpoints (2)

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.

Other (unclassified)

2 endpoints
Primary/protocol endpoint/low confidence

Metabolic improvement from baseline as measured by percentage reduction of body weight and reduction in liver steatosis from baseline as measured by percentage reduction in Fibroscan controlled attenuation parameter (CAP) score.

Time frame:Change from baseline to week 12

percent change from baseline, improvement

componentsBody weight, % change, liver steatosis cap pct change

Secondary/protocol endpoint/low confidence

Reduction from baseline in - 1) Liver steatosis as measured by MRI spectroscopy, 2) MRI visceral fat, 3) Liver enzymes (ALT, AST, GGT), 4) Drinking behaviors/cravings, 5) WHO risk drinking level

Time frame:Change from baseline to week 12

change from baseline, improvement

componentsLiver fat content, change, Visceral fat, change, ALT, change, AST, change, γ-GT, change, Alcohol consumption, change

Publications (1)

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.

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.