* 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.
