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Review
. 2024 Nov 11;23(1):45.
doi: 10.1186/s12991-024-00527-9.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) as treatment for nicotine cessation in psychiatric populations: a systematic review

Serene Lee #  1   2 , Maggie Li #  1 , Gia Han Le  1   3   4 , Kayla M Teopiz  1 , Maj Vinberg  5   6 , Roger Ho  7   8   9 , Hezekiah C T Au  1 , Sabrina Wong  1   3   10 , Kyle Valentino  1   10 , Angela T H Kwan  1   11 , Joshua D Rosenblat  3   4   10   12 , Roger S McIntyre  13   14   15
Affiliations
Review

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) as treatment for nicotine cessation in psychiatric populations: a systematic review

Serene Lee et al. Ann Gen Psychiatry. .

Abstract

Background: Nicotine use and nicotine use disorder (NUD) are the leading causes of preventable death in the United States. Persons with mental disorders (e.g., bipolar disorder) are differentially susceptible to nicotine use. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity and show preliminary evidence of efficacy in addiction-related behaviours. Herein, we synthesize extant preclinical and clinical evidence evaluating the effect of GLP-1RAs on neurobiological systems and behaviours salient to nicotine consumption and cessation.

Methods: Online databases (MedLine, Embase, AMED, PsychINFO, JBI EBP Database, PubMed, Web of Science, Google Scholar) were searched from inception to May 21, 2024. Relevant studies were also extracted from the reference lists of the obtained articles. All articles were screened against inclusion and exclusion criteria.

Results: Administration of GLP-1RAs reduced nicotine self-administration and nicotine-seeking behaviour in animal models that, in some cases, is sustained beyond exposure to the agent. GLP-1RAs also mitigated post-nicotine cessation weight gain, craving, withdrawal, and hyperphagia. The preceding effects are attributable to modulation of reward-related brain regions (e.g., mesolimbic dopamine system), resulting in nicotine aversion. GLP-1RAs were also efficacious as adjunctive therapies [e.g., in combination with nicotine replacement therapies (NRTs)].

Conclusion: The multi-effect characteristics in NUD paradigms provide a compelling rationale for large, adequately powered, long-term, randomized controlled trials of GLP-1RAs in the treatment and prevention of NUD. The replicated effect on mitigating post-nicotine cessation weight gain is a differentiating feature of GLP-1RAs from extant proven therapies for NUD.

Keywords: Dulaglutide; Exenatide; GLP-1; Liraglutide; Lixisenatide; Nicotine; Nicotine use disorder; Semaglutide; Tirzepatide.

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Conflict of interest statement

Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests Dr. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, Atai Life Sciences. Dr. Roger S. McIntyre is a CEO of Braxia Scientific Corp. Maj Vinberg has received consultancy fees from Lundbeck Pharma and Janssen Cilag within the last three years. Kayla M. Teopiz has received fees from Braxia Scientific Corp. Dr. Roger Ho has received funding from the National University of Singapore iHeathtech Other Operating Expenses (A-0001415-09-00). Dr. Joshua D. Rosenblat has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services Inc (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion and COMPASS.

Figures

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PRISMA flow diagram
See this image and copyright information in PMC

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