GLP-1 Receptor Agonists to Decrease Ethanol and CVD Risk in HIV (GL1DER HIV RCT)

GLP-1 Receptor Agonists to Decrease Ethanol and CVD Risk in HIV - GL1DER HIV RCT

The goal of this clinical trial is to learn if the drug semaglutide works to reduce alcohol intake among adults living with HIV. The main questions it aims to answer are:

1. Does semaglutide lower the average number of alcoholic beverages participants drink per week?
2. Does semaglutide lower the average number of cigarettes participants smoke per day?
3. Does semaglutide decrease the risk for cardiovascular disease among people living with HIV who drink alcohol and/or smoke tobacco?

Researchers will compare the effects of semaglutide to a placebo (a look-alike substance that contains no drug) to see if semaglutide works to lower the alcohol intake among participants each week.

Participants will:

1. Take semaglutide for 3 months
2. Visit the research clinic 3 times for checkups and tests
3. Provide blood samples, stool samples, and saliva samples for tests.

Study Overview

• Status: Recruiting
• Conditions: HIV; Alcohol; Cardiovascular Disease Prevention; Smoking Cigarette
• Intervention / Treatment: Drug: Semaglutide (Rybelsus®); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hilary A Tindle, MD, MPH; Phone Number: 615-875-9726; Email: hilary.tindle@vumc.org
• Study Contact Backup: Name: Rachel Jones, MS; Phone Number: 615-421-3508; Email: rachel.l.jones3@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Rachel Jones, MS; Phone Number: 615-421-3508; Email: rachel.l.jones3@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 18-89
• Prior diagnosis of HIV-1
• Affiliated with Vanderbilt Comprehensive Care Clinic
• On current ART regimen for at least 90 days prior to study entry with no missed doses for at least 7 consecutive days.
• Most recent absolute CD4 count ≥ 300 cells/mm3 and drawn within 12 months of study enrollment
• BMI ≥ 23 (calculated at screening)
• Self-report of consuming alcohol in past 90 days
• AUDIT-C ≥ 3 (male)/ ≥ 2 (female)
• Has an established stable address at which they can receive mail and can be reached for the next 6 months
• Willing and able to complete study procedures and follow-ups

Exclusion Criteria:

• Known allergy to semaglutide
• Currently taking GLP-1 RA (in the past 3 months)
• History of diabetes defined by diagnosis in Problems List in medical record
• History of pancreatitis
• History of gastroparesis
• Gallbladder disease (in the past 3 months)
• History of medullary thyroid carcinoma
• Family history of medullary thyroid carcinoma
• History of multiple endocrine neoplasia syndrome type 2
• Family history of multiple endocrine neoplasia syndrome type 2
• Cognitive inability to consent
• Barrier to speaking, hearing, reading, or writing English
• Pregnant or breastfeeding, or planning to become pregnant in the next 6 months
• Too ill to complete study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo study product
Experimental: Semaglutide; drug intervention	Drug: Semaglutide (Rybelsus®); experimental study medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average drinks/week past 30 days at 3 months	Average drinks/week past 30 days (via Timeline Follow Back (TLFB))	3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average cigarettes per day (cpd) past 30 days at 3 months	Average cigarettes per day in the past 30 days (via TLFB)	3 Months
Systemic inflammation (IL-6) at 3 months	Biomarker of systemic inflammation, Biomarker of gut permeability, Reynolds Risk Score, Mortality risk	6 Months

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); University of Louisville; Norton Healthcare
• Investigators: Principal Investigator: Hilary A Tindle, MD, MPH, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: October 23, 2025
• First Submitted That Met QC Criteria: October 23, 2025
• First Posted (Actual): October 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HIV; cardiovascular disease; alcohol; smoking; tobacco
• Additional Relevant MeSH Terms: Behavior; Tobacco Smoking; Tobacco Use; Cardiovascular Diseases; Smoking; Cigarette Smoking; semaglutide
• Other Study ID Numbers: 1P60AA032176 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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