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Clinical reports suggest diabetes and obesity drugs like Ozempic and Wegovy may reduce addictive behaviors

April 3rd, 2024 Christian S. Hendershot, Michael P. Bremmer, & Klara R. Klein

Long-acting glucagon-like peptide 1 (GLP-1) receptor agonists, including semaglutide (Ozempic, Wegovy) and tirzepatide (a dual GLP-1 and glucose-dependent insulinotropic polypeptide [GIP] receptor agonist marketed as Mounjaro and Zepbound) are part of a broader class of therapies known as incretin mimetics. GLP-1 receptor agonists (also known as GLP-1 analogues) were designed to mimic human GLP-1, an endogenous neuropeptide and incretin hormone that stimulates insulin release and promotes satiety. GLP-1 analogues were initially developed based on the structure of exendin-4, a peptide isolated from the saliva of the Gila monster, a lizard native to the American Southwest and Mexico that can withstand long periods without eating. The ability of GLP-1 receptor agonists to lower blood glucose led to their development as diabetes treatments. The potency of these agents for promoting satiety and weight loss later resulted in U.S. Food and Drug Administration (FDA) approvals for the indication of weight reduction, beginning with liraglutide (Saxenda, in 2014) and followed by semaglutide (Wegovy, in 2021) as well as tirzepatide (Zepbound, in 2023).

Although GLP-1 receptor agonists have been prescribed for roughly two decades, increasing attention to the potent weight loss properties of long-acting agents—and recent FDA approvals of Wegovy and Zepbound for weight loss—have led to skyrocketing demand, rendering these therapies household names. By the end of 2023, Science deemed long-acting GLP-1 receptor agonists the "Breakthrough of the Year," whereas The New Yorker dubbed 2023 "The Year of Ozempic" (Khullar, 2023). There is good reason for these declarations. The extraordinary efficacy of long-acting GLP-1 receptor agonists has drastically changed the treatment of metabolic disorders—at the same time generating astronomical profits (the market valuation of Novo Nordisk, the Danish company that patented Ozempic and Wegovy, now exceeds the value of Denmark's gross domestic product). Based on this unprecedented success, numerous pharmaceutical companies have newer GLP-1 receptor agonists and related incretin therapies at various stages of development.

Potential implications of incretin therapies for addictive behaviors

The surging popularity of semaglutide and tirzepatide has also highlighted other potential clinical applications of GLP-1 receptor agonists, one being for the treatment of substance use disorders. Over the last year, numerous media stories detailed unanticipated reductions in alcohol use or other addictive behaviors among those treated with long-acting GLP-1 receptor agonists. Although such anecdotal observations had been noted earlier, the steep increase in prescriptions of GLP-1 receptor agonists (particularly following the FDA's approval of semaglutide for weight loss) brought this topic to broad public attention early in 2023 (Blum, 2023). Although years of nonhuman animal research had already shown that GLP-1 analogues can suppress the intake and reward value of addictive drugs (Jerlhag, 2023), the novelty of these clinical reports prompted excitement that the pharmaceutical industry had unwittingly developed a new class of addiction treatments (Zhang, 2023). At the time the media reports began to accumulate, only one trial had tested the effects of a GLP-1 receptor agonist (exenatide, a synthetic analogue of exendin-4) on human drinking behavior (Klausen et al., 2022), leaving public discussions to rely heavily on anecdotal reports.

Social media and clinical reports offer clues about real-world experiences

To examine anecdotal evidence in more detail, our recent report in the Journal of Studies on Alcohol and Drugs (Bremmer & Hendershot, 2024) collated information from a highly accessible source: Reddit forums. Reddit threads focusing on personal experiences with semaglutide and tirzepatide were "scraped" for alcohol-related content and qualitatively coded, generating a collective snapshot of alcohol-related experiences during treatment. Coding of the reports showed that reductions in alcohol use were commonly reported and often described as substantial. Users reported a variety of phenomenological experiences coinciding with drinking reductions, including diminished wanting/craving for alcohol, reduced pleasurable effects from alcohol, increases in aversive responses to alcohol, and changes in drinking "topography," among others. Of note, many reported simply losing interest in drinking alcohol—or not needing to continue drinking after starting—pointing to alcohol satiety as one explanation for reduced drinking (Bremmer & Hendershot, 2024). Reported experiences differed across users (with some reporting no changes), suggesting individual differences. Not surprisingly, many aspects of these reports align with known effects of GLP-1 receptor agonists on hunger, food motivation and reward, and feeding. While conducting early studies of semaglutide in substance use disorder (SUD) populations, our team has received numerous unsolicited reports from patients and clinicians who recount similar observations.

Recent speculation that incretin-based therapies could eventually be repurposed for the treatment of SUD has sparked considerable public and media attention, already leading some to seek out these agents as "off-label" treatments for SUD. Because early trials of semaglutide and other long-acting GLP-1 receptor agonists for SUD are only recently underway, off-label use is premature and the public should be reminded that FDA-approved medications are already available (Leggio et al., 2023). Nonetheless, anecdotal and clinical reports can be considered an early form of "front-line" evidence worth attending to. Optimistically, such reports might anticipate future efforts to repurpose incretin-based therapies for SUD, a development that could bring substantial public health benefits. While awaiting results from controlled studies, observational and phenomenological reports should encourage greater clinical and research attention to questions of whether, why, and in which populations long-acting GLP-1 receptor agonists might reduce alcohol and other drug use. If research findings align with clinical and anecdotal reports, "The Year of Ozempic" might mark the beginning of an interesting time for addiction science.

References

Blum, D. (2023, February 24). Some people on Ozempic lose the desire to drink. Scientists are asking why. The New York Times. https://www.nytimes.com/2023/02/24/well/eat/ozempic-side-effects-alcohol.html

Bremmer, M. P., & Hendershot, C. S. (2024). Social media as pharmacovigilance: The potential for patient reports to inform clinical research on glucagon-like peptide 1 (GLP-1) receptor agonists for substance use disorders. Journal of Studies on Alcohol and Drugs, 85(1), 5–10. https://doi.org/10.15288/jsad.23-00318

Jerlhag, E. (2023). The therapeutic potential of glucagon-like peptide-1 for persons with addictions based on findings from preclinical and clinical studies. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1063033

Khullar, D. (2023, December 14). The year of Ozempic. The New Yorker. https://www.newyorker.com/culture/2023-in-review/the-year-of-ozempic

Klausen, M. K., Jensen, M. E., Møller, M., Le Dous, N., Jensen, A.-M. Ø., Zeeman, V. A., Johannsen, C.-F., Lee, A., Thomsen, G. K., Macoveanu, J., Fisher, P. M., Gillum, M. P., Jørgensen, N. R., Bergmann, M. L., Enghusen Poulsen, H., Becker, U., Holst, J. J., Benveniste, H., Volkow, N. D., . . . Fink-Jensen, A. (2022). Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight, 7(19). https://doi.org/10.1172/jci.insight.159863

Leggio, L., Hendershot, C. S., Farokhnia, M., Fink-Jensen, A., Klausen, M. K., Schacht, J. P., & Simmons, W. K. (2023). GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders. Nature Medicine, 29(12), 2993–2995. https://doi.org/10.1038/s41591-023-02634-8

Zhang, S. (2023, May 19). Did scientists accidentally invent an anti-addiction drug? The Atlantic. https://www.theatlantic.com/health/archive/2023/05/ozempic-addictive-behavior-drinking-smoking/674098/

More information:
Bremmer, M. P., & Hendershot, C. S. (2024). Social media as pharmacovigilance: The potential for patient reports to inform clinical research on glucagon-like peptide 1 (GLP-1) receptor agonists for substance use disorders. Journal of Studies on Alcohol and Drugs, 85(1), 5–10. doi.org/10.15288/jsad.23-00318
To arrange an interview with Christian Hendershot, please email him at christian_hendershot@med.unc.edu.
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Citation: Clinical reports suggest diabetes and obesity drugs like Ozempic and Wegovy may reduce addictive behaviors (2024, April 3) retrieved 4 May 2024 from https://sciencex.com/wire-news/473615805/clinical-reports-suggest-diabetes-and-obesity-drugs-like-ozempic.html

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