Impact of GLP-1 Receptor Agonist Therapy on Alcohol Pharmacokinetics

Participants will:

• Arrive to study visit in a fasted state
• Provide blood, breath, and urine samples prior to intervention
• Complete baseline cognitive assessments
• Self-administer the intervention (time 0), followed by breakfast (time 30 minutes)
• Complete subjective and cognitive assessments throughout treatment visit
• Provide blood, breath, and urine samples throughout treatment visit
• Consume lunch 260 minutes after dosing
• Complete study visit at 360 minutes
• Complete a final study survey

Primary Objective: Characterize the pharmacokinetics of ethanol in participants receiving maintenance Glucagon-like peptide-1 (GLP-1) receptor agonist (RA) therapy (tirzepatide).

Secondary Objectives:

• Determine the effects of GLP-1 RA therapy on alcohol-induced impairment, as measured by

• objective performance
• subjective impairment assessments
• risk perception

Correlative Objectives

• Define the exposure-response relationship between biological alcohol concentrations (breath and blood) and functional impairment to determine if Primary Objective
• Characterize the pharmacokinetics of ethanol in participants receiving maintenance GLP-1 RA therapy (tirzepatide).

Inclusion criteria

• At least 21 years of age, no older than 55 years of age
• BMI 30-45 kg/m2
• Taking stable dose of prescribed, branded tirzepatide for at least 28 days
• Self-reported regular alcohol consumption
• Good mental health as determined by self-reported responses to the Psychopathology Screener and review by Study Physician as necessary
• Absence of any major medical, cardiovascular, endocrine, and neurological condition as determined by self-reported responses to the Medical History Screener
• In possession of a valid drivers' license with at least two years of driving experience
• English-speaking (able to provide consent and complete questionnaires)
• Written Informed Consent

Exclusion criteria

• AUDIT score of >8 requires Study Physician review
• Use of compounded GLP-1 RA
• History of or current substance use disorder as determined by self-reported responses to the Internalizing, Externalizing, and Substance Use Disorder Screener, Drug Use Disorders Identification Test, Alcohol Use Disorder Identification Test
• Pregnancy or lactation (pregnancy test, if needed)
• Use of medications that may impact cognitive ability or potentiate alcohol (e.g., mood stabilizers, sedatives)
• Use of medications that are known to significantly delay gastric emptying as determined by Study Physician
• History of pancreatitis, severe gastroparesis, or personal or family history of medullary thyroid or multiple endocrine neoplasia syndrome type 2