Report on the Off-Label Use of GLP-1 Agonists for Addiction Treatment and Implications for Sustainable Development Goals

This report details an innovative clinical initiative at Caron Treatment Centers involving the off-label prescription of Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, for substance use disorders. This approach is examined through the lens of the United Nations Sustainable Development Goals (SDGs), primarily SDG 3 (Good Health and Well-being).

The Public Health Crisis of Addiction and its Relation to SDG 3

The ongoing crisis of addiction, with approximately 250,000 annual deaths in the United States from drug overdoses and alcohol-related causes, represents a significant challenge to achieving SDG 3: Good Health and Well-being. Existing treatments for substance use disorders are often underutilized or have limited efficacy, highlighting a critical need for innovation to meet SDG Target 3.5, which aims to strengthen the prevention and treatment of substance abuse.

• Current medication-assisted treatments for opioid addiction, such as buprenorphine and methadone, face significant stigma.
• Pharmacological options for alcohol use disorder, like naltrexone, offer only marginal benefits.
• There are no approved medication treatments for stimulant addictions, including methamphetamine or cocaine.

An Innovative Clinical Approach at Caron Treatment Centers

Caron Treatment Centers, a nonprofit rehabilitation facility, has initiated a program prescribing GLP-1 medications off-label to address a range of substance and behavioral addictions. This represents a potential paradigm shift in addiction medicine, moving beyond the medications’ approved use for diabetes and obesity.

Pioneering Off-Label Application

Physicians at Caron are prescribing semaglutide to treat addictions to opioids, alcohol, and stimulants, as well as behavioral addictions like gambling. This practice is based on anecdotal evidence and clinical observation that these medications significantly reduce or “obliterate” patient cravings. The physicians leading this initiative have personal experience with addiction and recovery, providing a unique perspective on treatment efficacy.

Protocol and Implementation

The protocol at Caron differs from standard obesity treatment, utilizing lower doses and often relying on compounded versions of the medication to manage costs and access, a key consideration for SDG Target 3.8 (access to affordable essential medicines).

1. The initiation dose is 0.25 mg, potentially increasing to 0.5 mg, which is significantly lower than typical doses for weight management.
2. As of July 2024, 229 patients had received a GLP-1 medication, with 47 receiving it specifically for addiction under the new program.
3. The initiative is currently run as a “clinical initiative” to gather data, not a formal clinical trial.

Alignment with Sustainable Development Goals

The use of GLP-1s for addiction treatment directly intersects with several key SDG targets, offering both promise and challenges.

SDG 3: Good Health and Well-being

This initiative is a direct effort to advance global health targets by introducing a novel treatment for a major public health issue.

• Target 3.5 (Substance Abuse): The program offers a new pharmacological tool to strengthen addiction treatment, potentially improving recovery rates and reducing substance-related harm.
• Target 3.4 (Non-communicable Diseases and Mental Health): By treating addiction, which is a mental health disorder, and its frequent comorbidity with obesity (a non-communicable disease), the intervention addresses multiple facets of this target.
• SDG 9 (Industry, Innovation, and Infrastructure): The repurposing of GLP-1s represents a significant medical innovation. However, the lack of formal clinical trials highlights the need for greater investment in research infrastructure to validate such findings.

SDG 10: Reduced Inequalities

While innovative, the context of the Caron program raises concerns about equitable access to treatment, a core principle of SDG 10.

• High Cost of Treatment: Treatment at the elite Caron facility can cost between $30,000 and $65,000, making it inaccessible to the vast majority of individuals with substance use disorders.
• Disparity in Access: The success observed at a well-resourced, inpatient facility with comprehensive support may not be replicable in less-controlled, community-based settings where the burden of addiction is highest.
• Reliance on Compounded Drugs: The use of cheaper, compounded semaglutide underscores the affordability barrier of brand-name medications, but this access is threatened by potential FDA regulatory changes.

Challenges and Future Outlook

The long-term viability and scalability of using GLP-1s for addiction face significant scientific, regulatory, and financial hurdles.

Scientific and Regulatory Hurdles

The optimism of clinicians at Caron is tempered by the current landscape of addiction science and regulation.

1. Lack of Clinical Data: The practice is ahead of rigorous scientific evidence. Formal clinical trials are underway but results are not expected for at least two years.
2. Potential Side Effects: Gastrointestinal discomfort is a known side effect and led to a high dropout rate in one small study of GLP-1s for opioid use disorder. The impact on patients without obesity, such as malnutrition or muscle loss, requires further study.
3. Regulatory and Insurance Barriers: Without FDA approval for an addiction indication, insurers are unlikely to cover the high cost of brand-name GLP-1s for this purpose, perpetuating the access and inequality issues central to SDG 10.

Conclusion

The initiative at Caron Treatment Centers represents a promising, albeit preliminary, step towards a new frontier in addiction medicine that could significantly advance SDG 3. The observed reduction in cravings for substances and harmful behaviors suggests a powerful new tool may be on the horizon. However, for this innovation to contribute meaningfully to global health goals, it must be validated by robust scientific research and made accessible and affordable for all populations, thereby addressing the critical challenges of health equity outlined in SDG 10.

Which SDGs are addressed or connected to the issues highlighted in the article?

SDG 3: Good Health and Well-being

• The article’s central theme is the treatment of substance use disorders and other addictions, which directly aligns with ensuring healthy lives and promoting well-being. It explores innovative treatments for addictions to substances like alcohol, opioids, and stimulants, as well as behavioral addictions such as gambling and overeating (food addiction).
• It highlights the significant public health crisis of addiction, stating that a “combined 250,000 Americans dying each year from drug overdose and alcohol-related causes.”
• The article also discusses the use of GLP-1 medications for obesity, a major non-communicable disease. Dr. Klein’s personal story of using the medication to “drop 40 pounds” and the mention of patients with a “BMI above 30” connect the topic to broader health and wellness issues beyond substance abuse.

What specific targets under those SDGs can be identified based on the article’s content?

SDG 3: Good Health and Well-being

1. 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 a new approach to treating substance abuse. The Caron Treatment Centers are pioneering the off-label use of GLP-1 medications (semaglutide) to “help treat the addictions that brought them here in the first place,” including “alcohol, or opioids.” The article explicitly states the goal is to find better treatments for substance use disorders, noting that existing medications are “marginally effective or sorely underutilized.”

2. 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.

   Substance use disorder is a critical mental health condition. The article directly addresses premature mortality by citing the “250,000 Americans dying each year from drug overdose and alcohol-related causes.” The new treatment aims to reduce cravings and support long-term sobriety, thereby preventing these deaths. Furthermore, the treatment’s original purpose is to address obesity (“obesity is an addiction to food”), a key risk factor for many non-communicable diseases. By treating obesity, the medication also contributes to the prevention of NCDs.

3. Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases… provide access to affordable essential medicines…

   The article discusses the innovative, yet scientifically unproven, nature of this treatment. It notes that Caron is in “uncharted territory” and that “only a handful of clinical trials are underway.” This highlights the need for more research and development (R&D). The article also addresses the issue of access and affordability. It mentions the high cost of treatment at Caron (“as much as $65,000 for a premium package”) and the reliance on “cheap, compounded versions of the medications” because brand-name drugs are expensive and not covered by insurance for this off-label use.

Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

SDG 3: Good Health and Well-being

1. Indicators for Target 3.5 (Treatment of substance abuse):
   • Coverage of treatment interventions: The article describes the Caron program as a “clinical initiative” providing treatment. The number of patients receiving the treatment (“229 Caron patients have received a GLP-1 since the start of 2024”) serves as a direct indicator of treatment coverage within this specific program.
   • Patient-reported outcomes: While anecdotal, the article implies progress is measured by patient outcomes. It mentions that for some patients, cravings are “obliterated,” and “periods of sobriety are getting longer and longer.” These are qualitative indicators of treatment effectiveness.
2. Indicators for Target 3.4 (Mortality from NCDs and mental health):
   • Mortality rate attributed to substance abuse: The statistic of “250,000 Americans dying each year from drug overdose and alcohol-related causes” is a direct indicator of premature mortality that this treatment aims to reduce.
   • Prevalence of obesity: The article mentions Body Mass Index (BMI) as a criterion for treatment, noting that “70% [of a specific patient group] have a BMI above 30.” Tracking BMI and weight loss (like Dr. Klein’s 40-pound weight loss) are indicators of progress against the non-communicable disease of obesity.
3. Indicators for Target 3.b (R&D and access to medicines):
   • Investment in R&D: The article implies a lack of formal R&D by stating Caron’s program is a “clinical initiative” and not a “formal study” or “clinical trial.” The number of active clinical trials (“a handful”) is an indicator of the current state of research.
   • Affordability and availability of medicines: The article points to significant access barriers. Indicators include the high out-of-pocket cost of treatment (“$30,000 for a standard one-month course”), the lack of insurance reimbursement for this use, and the reliance on “cheap, compounded versions” as an alternative to “high-priced injector pens.”

SDGs, Targets, and Indicators Analysis

Source: statnews.com