Does Semaglutide Reduce Alcohol Intake in Patients With Alcohol Use Disorder and Comorbid Obesity?

Inclusion Criteria:

• Informed oral and written consent

• Diagnosed with alcohol dependence according to the criteria of the InternationalClassification of Diseases 10 (ICD-10), and diagnosed with alcohol use disorderaccording to the Diagnostic and Statistical Manual of Mental Disorders, FifthEdition (DSM-5)

• Alcohol use disorder identification test (AUDIT) score >15

• Body mass index (BMI) above or equal to 30 kg/m2

• Age 18 - 70 years (both included)

• Heavy alcohol drinking defined as more than 6 days with alcohol consumption over 4units (48 g alcohol) for women and 5 units (60 g alcohol) for men during aconsecutive 30-day period, within 40 days prior to baseline evaluation, measured bythe TLFB method. The 30-day period will be the 30 consecutive days with the biggestalcohol intake (most heavy drinking days and the largest amount of total alcohol)out of the 40 days.

Exclusion Criteria:

• Severe psychiatric disease, defined as a diagnosis of schizophrenia, paranoidpsychosis, bipolar disorder or mental retardation

• A history of delirium tremens or alcohol withdrawal seizures

• No serious withdrawal symptoms at inclusion (a score higher than 9 on the ClinicalInstitute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)) at baselineexaminations

• Present or former neurological disease, including traumatic brain injury

• Type 1 diabetes, type 2 diabetes in poor glycaemic control (defined as HbA1c ≥48mmol/l or fasting plasma glucose above 7.0 mmol/l at inclusion)

• Females of childbearing potential who are pregnant, breast-feeding or have theintention of becoming pregnant within the next 9 months (26 weeks plus two monthsafter discontinuation of semaglutide), or are not using contraceptives (during thewhole study period) considered as highly effective (combined (oestrogen andprogestogen containing) hormonal contraception associated with inhibition ofovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraceptionassociated with inhibition of ovulation (oral, injectable, implantable) intrauterinedevice, bilateral tubal occlusion, vasectomised partner, sexual abstinence).

• Pregnancy (serum human chorionic gonadotropin (hCG) > 3 U/L at inclusion)

• Impaired hepatic function (liver transaminases >3 times the upper limit)

• Impaired renal function (eGFR < 50 ml/min and/or plasma creatinine >150 μmol/l)

• Impaired pancreatic function (any history of acute or chronic pancreatitis and/oramylase > 2 times upper limit)

• Former medullary thyroid carcinoma (MTC) and/or family history with MTC and/orMultiple Endocrine Neoplasia syndrome type 2 (MEN 2)

• Cardiac problems defined as decompensated heart failure (NYHA class III or IV),unstable angina pectoris and/or myocardial infarction within the last 12 months

• Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic bloodpressure >110 mmHg)

• Concomitant pharmacotherapy against alcohol use disorder, i.e., disulfiram,naltrexone, acamprosate, or nalmefene, since the first of the 30 drinking daysregistered for inclusion at the TLFB-schedule.

• Receiving any investigational drug within the last three months

• Use of weight-lowering pharmacotherapy within the preceding 3 months

• Any other active substance use defined as a DUDIT-score >1 (except nicotine)

• Hypersensitivity to the active substance or any of the excipients

• Only for patients undergoing brain scans: o Contraindications for undergoing an MRI scan (magnetic implants, pacemaker,claustrophobia, etc.)

• Unable to speak and/or understand Danish

• Any condition that the investigator feels would interfere with trial participation