Report on a Phase 2 Clinical Trial of Semaglutide for Alcohol Use Disorder and its Implications for Sustainable Development Goals

Introduction: Addressing Alcohol-Related Harm in the Context of SDG 3

A preliminary phase 2 clinical trial has demonstrated the potential of semaglutide, a GLP-1 receptor agonist, in reducing alcohol consumption and craving among individuals with Alcohol Use Disorder (AUD). This research is critically relevant to the United Nations Sustainable Development Goals (SDGs), particularly SDG 3, which aims to ensure good health and well-being for all. The harmful use of alcohol, responsible for an estimated 2.6 million deaths annually worldwide, is a significant barrier to achieving key health targets.

This study directly addresses two specific targets within SDG 3:

• Target 3.5: Strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.
• Target 3.4: Reduce by one-third premature mortality from non-communicable diseases (NCDs) through prevention and treatment. Excess alcohol consumption is a major risk factor for NCDs such as heart disease, liver disease, and cancer.

The current treatment landscape for AUD is inadequate, with only three FDA-approved medications and low rates of treatment uptake. This investigation into repurposing existing medications like semaglutide represents a vital step toward developing more effective and accessible interventions, aligning with the global commitment to combat substance abuse and its health consequences.

Clinical Trial Methodology

The randomized clinical trial, led by researchers at the University of Southern California, was designed to provide initial evidence for the efficacy of semaglutide in treating AUD. The study’s design and participant characteristics are outlined below.

Participant Profile

• Sample Size: 48 participants recruited at the University of North Carolina, Chapel Hill.
• Demographics: 71% female, with an average age of approximately 40 years.
• Diagnosis: All participants met the criteria for AUD within the prior year.
• Key Inclusion Criteria: Participants were not actively seeking or attempting to reduce their alcohol consumption, providing insight into the medication’s effect on a non-treatment-seeking population. About half of the participants had a Body Mass Index (BMI) of 30 or higher, consistent with the medical definition of obesity.

Trial Procedure

The trial was conducted over nine weeks, with participants randomly assigned to one of two groups:

1. Treatment Group: Received weekly injections of semaglutide, with the dose escalating from 0.25 mg to 1.0 mg over the course of the trial.
2. Control Group: Received weekly placebo injections.

Data was collected through two primary methods: objective laboratory sessions measuring voluntary alcohol consumption and daily self-reported logs tracking drinking patterns, heavy drinking days, and cravings.

Key Findings and Contribution to SDG Targets

The trial yielded encouraging results, indicating that semaglutide may be an effective tool in achieving the objectives of SDG 3.5. Compared to the placebo group, participants treated with semaglutide demonstrated statistically significant improvements.

• Reduced Consumption: Participants took significantly fewer drinks on days they consumed alcohol and showed greater reductions in the number of heavy drinking days.
• Reduced Craving: The treatment group reported significantly lower levels of weekly alcohol craving throughout the trial.
• Objective Confirmation: In laboratory settings, the medication group showed greater reductions in alcohol consumption, providing an objective measure that supports the self-reported data.
• Dose-Response Relationship: The beneficial effects of the medication were more pronounced at a higher dose (0.5mg/week vs. 0.25mg/week), suggesting a clear dose-sensitivity.

These findings are promising, as the observed effect sizes on heavy drinking are comparable to or greater than those of existing FDA-approved AUD treatments. By reducing heavy drinking, this intervention could directly contribute to the prevention of NCDs, supporting the aims of SDG 3.4.

Implications for Public Health and Future Directions

The results of this trial suggest that repurposing GLP-1 agonists like semaglutide could be a viable strategy for addressing the public health crisis of AUD. The medication was well-tolerated and showed efficacy in a population not actively seeking to reduce drinking, which is significant given that less than 10% of individuals with AUD receive treatment.

This approach aligns with SDG 3.8 (Achieve universal health coverage…and access to safe, effective, quality and affordable essential medicines), as leveraging widely available, safety-tested drugs could accelerate the availability of new treatment options. The findings suggest semaglutide may be particularly useful for individuals seeking to reduce harmful consumption rather than achieve total abstinence.

The research team acknowledges the study’s limitations, including its small scale and short duration. To fully validate these preliminary findings and inform clinical practice and health policy, larger and longer-term controlled trials are necessary. Future research should investigate multiple GLP-1-based medications in diverse populations, including those with severe AUD, to solidify a path toward meeting global health goals related to the harmful use of alcohol.

SDGs Addressed

SDG 3: Good Health and Well-being

• The article’s central theme is Alcohol Use Disorder (AUD), a significant health issue. It discusses the high mortality rates associated with alcohol consumption, stating, “In the U.S., an estimated 178,000 deaths per year are attributed to alcohol consumption, and 2.6 million deaths annually worldwide.”
• It explores a potential new pharmacological treatment (semaglutide) to combat AUD, directly aligning with the goal of ensuring healthy lives and promoting well-being.
• The text links excessive alcohol use to major non-communicable diseases like “heart and liver diseases and cancer,” which are primary targets for global health initiatives.

Specific Targets

1. Target 3.4: By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.

   • The article directly connects alcohol consumption to non-communicable diseases, noting it is “clearly linked to health problems, including many of the major public health threats facing Americans: heart and liver diseases and cancer among them.”
   • The clinical trial for semaglutide represents an effort to improve treatment, which is a key component of reducing mortality from these diseases. The potential of the drug to reduce heavy drinking could serve as a preventive measure against the long-term development of such conditions.

2. Target 3.5: Strengthen the prevention and treatment of substance abuse, including narcotic drug abuse and harmful use of alcohol.

   • The article is entirely focused on addressing the “harmful use of alcohol.” It defines AUD as “a pattern of alcohol use that involves problems controlling your drinking.”
   • It highlights a significant gap in treatment, stating, “less than 10% of those with AUD report past-year treatment, of whom less than 2% have taken medicines for it.”
   • The research on semaglutide is presented as a response to the “great unmet need for new medicines to treat alcohol-related problems,” directly aiming to strengthen treatment options for substance abuse.

Indicators

1. Indicator 3.4.1: Mortality rate attributed to cardiovascular disease, cancer, diabetes or chronic respiratory disease.

   • The article provides explicit mortality data linked to alcohol, a major risk factor for these diseases: “In the U.S., an estimated 178,000 deaths per year are attributed to alcohol consumption, and 2.6 million deaths annually worldwide.” This data is used to measure the scale of the problem that new treatments aim to solve.

2. Indicator 3.5.1: Coverage of treatment interventions (pharmacological, psychosocial and rehabilitation and aftercare services) for substance use disorders.

   • The article implies this indicator by providing statistics on the lack of treatment coverage: “Yet less than 10% of those with AUD report past-year treatment, of whom less than 2% have taken medicines for it.” The development of new, more effective, or more appealing drugs like semaglutide could increase this coverage rate.

3. Indicator 3.5.2: Harmful use of alcohol… and the proportion of the population with alcohol use disorders.

   • The article provides specific data on the prevalence of AUD: “In the U.S., 29% of adults meet conditions for an AUD diagnosis over their lifetime and an estimated 11% in the most recent year.”
   • The clinical trial’s success is measured by metrics that directly relate to reducing the harmful use of alcohol, such as “greater reductions in heavy drinking days” and a reduction in the “quantity of alcohol consumed.” These are objective measures of progress toward this indicator.

Summary Table

Source: bbrfoundation.org