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

The goal of GL1DER 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: 

• Does semaglutide lower the average number of alcoholic beverages participants drink per week? 
• Does semaglutide lower the average number of cigarettes participants smoke per day? 
• 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:

• Take semaglutide for three months.
• Visit the research clinic three times for checkups and tests.
• Provide blood samples, stool samples, and saliva samples for tests. 

Background

Unhealthy alcohol consumption and cigarette smoking are leading causes of cardiovascular disease (CVD) and death, often co-occur, and are common among people with HIV (PWH) who bear a two-fold excess risk of CVD compared to people without HIV. Further, PWH experience higher mortality at lower levels of alcohol consumption than people without HIV. Alcohol use, smoking, and HIV each independently elevate systemic inflammation and undermine cardiometabolic health via myriad pathways including dyslipidemia and increased visceral adiposity. 

While modestly effective therapies exist for smoking, few exist for alcohol use, and more effective therapies for alcohol consumption and smoking are urgently needed to reduce CVD risk and mortality among PWH. Glucagon-like peptide receptor agonists (GLP-1 RA) reduce insulin resistance and inflammation, promote weight loss, and prevent CVD in patients with and without diabetes, setting a new standard of care to improve cardiometabolic health in people at high risk of CVD. GLP-1 is produced in the gut and brainstem and GLP-1 receptors throughout brain regions underlie reward and motivation (e.g., ventral tegmental area, nucleus accumbens, medial habenula). In preclinical studies, GLP-1 RA attenuate rewarding effects of alcohol and nicotine and reduce consumption of these substances. 

Early clinical trials report that GLP-1 RA lower alcohol craving and consumption, promote smoking abstinence, and blunt weight gain after abstinence. There is a strong scientific premise to study GLP-1 RA for alcohol use, smoking, and CVD risk, but no trials have tested these outcomes in PWH. To address this critical gap, we propose the GLP-1 Receptor Agonists to Decrease Ethanol and CVD Risk in HIV (GL1DER HIV) RCT, a double-masked placebo-controlled RCT to assess efficacy of the potent oral GLP-1 RA semaglutide for 12 weeks among 200 PWH who drink alcohol, most of whom also smoke.

For more information on GL1DER, visit these pages:

• clinicaltrials.gov 
• NIH RePORTER