Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide and liraglutide, are licensed in the UK for managing type 2 diabetes and obesity. Emerging research has sparked interest in whether these medications might influence addictive behaviours, following observations that GLP-1 receptors exist in brain reward pathways. Whilst preclinical studies and early observational data suggest potential effects on substance use, it is crucial to emphasise that GLP-1 medications are not licensed or recommended for treating addiction in the UK. This article examines the current evidence, proposed mechanisms, clinical limitations, and practical guidance for patients and healthcare professionals.

What Are GLP-1 Medications and How Do They Work?

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications originally developed for the management of type 2 diabetes mellitus and, more recently, some have been approved for weight management. In the UK, these medications have specific licensed indications:

• Semaglutide: Available as Ozempic (for type 2 diabetes) and Wegovy (for weight management)

• Liraglutide: Available as Victoza (for type 2 diabetes) and Saxenda (for weight management)

• Dulaglutide: Available as Trulicity (for type 2 diabetes only)

GLP-1 is a naturally occurring incretin hormone released by the intestine in response to food intake. It plays a crucial role in glucose homeostasis by:

• Enhancing insulin secretion from pancreatic beta cells in a glucose-dependent manner

• Suppressing glucagon release, thereby reducing hepatic glucose production

• Slowing gastric emptying, which moderates postprandial glucose excursions

• Promoting satiety through actions on appetite centres in the brain

GLP-1 receptor agonists mimic these physiological effects but with extended half-lives, allowing for once-weekly or once-daily administration. The medications bind to GLP-1 receptors located not only in the pancreas and gastrointestinal tract but also in various brain regions, including areas involved in reward processing and appetite regulation.

Beyond their established metabolic benefits, emerging research has identified GLP-1 receptors in the mesolimbic dopamine system—the brain's reward pathway—which has sparked scientific interest in whether these medications might influence behaviours beyond eating, including addictive behaviours. This observation forms the basis for ongoing investigations into potential applications beyond diabetes and obesity management.

Current Evidence: GLP-1 Drugs and Addiction Research

The potential role of GLP-1 receptor agonists in modulating addictive behaviours represents an emerging area of research, though it is important to emphasise that there is no official indication or licence for these medications in treating addiction in the UK or elsewhere. Any use for addiction should be confined to clinical trials or specialist research settings.

Preclinical studies in animal models have demonstrated that GLP-1 receptor agonists can reduce the consumption of and preference for alcohol, as well as decrease drug-seeking behaviours for substances including cocaine, amphetamines, and nicotine. These findings have generated considerable scientific interest in translating such observations to human populations.

Observational human studies have provided preliminary signals that warrant further investigation. Several retrospective analyses of healthcare databases have suggested that individuals prescribed GLP-1 receptor agonists for diabetes or obesity may report reduced alcohol consumption compared to those on alternative treatments. A Swedish registry study published in 2023 found associations between GLP-1 agonist use and lower rates of hospitalisation for alcohol-related disorders, though such observational data cannot establish causation.

Small-scale clinical trials are now underway examining GLP-1 medications in alcohol use disorder and other substance dependencies. Early phase studies have shown mixed results. For example, a randomised controlled trial of exenatide in alcohol use disorder found benefits only in specific subgroups, highlighting the preliminary nature of this research. Most studies have small sample sizes and short follow-up periods.

It is crucial to recognise that this research is in its infancy. The National Institute for Health and Care Excellence (NICE) has not issued guidance on GLP-1 receptor agonists for addiction treatment, and these medications should not be considered established therapies for substance use disorders. Current evidence-based treatments for addiction—including psychological interventions, mutual support groups, and licensed pharmacotherapies—remain the standard of care.

Potential Mechanisms Behind GLP-1 Effects on Addictive Behaviours

Understanding the biological mechanisms through which GLP-1 receptor agonists might influence addictive behaviours requires examining the neuroanatomy of reward processing and how these medications interact with relevant brain circuits.

GLP-1 receptors are expressed in key reward-related brain regions, including:

• The ventral tegmental area (VTA) and nucleus accumbens, which form the core of the mesolimbic dopamine pathway

• The prefrontal cortex, involved in executive function and impulse control

• The amygdala, which processes emotional salience and stress responses

The prevailing hypothesis suggests that GLP-1 receptor activation may modulate dopamine signalling in reward circuits. Addictive substances typically cause supraphysiological dopamine release in the nucleus accumbens, reinforcing drug-seeking behaviour. Preclinical research suggests GLP-1 receptor agonists may influence this reward response, potentially affecting the reinforcing properties of addictive substances, though human evidence remains limited.

Additionally, these medications may influence stress and anxiety pathways. Chronic stress is a well-established trigger for relapse in substance use disorders, and GLP-1 signalling has been implicated in stress response regulation in animal models. By potentially modulating stress-induced craving, GLP-1 agonists might offer a dual mechanism of action, though this remains hypothetical in humans.

Another proposed mechanism involves impulse control and decision-making. GLP-1 receptors in the prefrontal cortex may enhance executive function, potentially improving an individual's ability to resist immediate gratification in favour of longer-term goals—a cognitive process often impaired in addiction.

It is important to note that these mechanisms remain theoretical and are based largely on preclinical research. The translation of these findings to clinical practice requires rigorous investigation through properly designed randomised controlled trials with appropriate outcome measures and safety monitoring.

Clinical Considerations and Limitations of Current Research

Healthcare professionals and patients should approach the potential use of GLP-1 receptor agonists for addiction with appropriate caution, recognising significant limitations in the current evidence base.

Methodological limitations of existing research include:

• Observational study designs that cannot establish causation—individuals prescribed GLP-1 agonists may differ systematically from comparison groups

• Confounding variables such as concurrent lifestyle interventions, psychological support, or other medications

• Short follow-up periods that do not capture long-term outcomes or relapse patterns

• Publication bias, with positive findings more likely to be reported than null results

Safety considerations are paramount. GLP-1 receptor agonists carry recognised adverse effects that must be weighed against any potential benefits:

• Gastrointestinal symptoms (nausea, vomiting, diarrhoea) occur commonly, particularly during dose escalation

• Risk of pancreatitis, though rare, requires clinical vigilance; treatment should be discontinued if pancreatitis is suspected

• Gallbladder disease including cholelithiasis and cholecystitis has been reported, particularly with weight loss

• Dehydration and acute kidney injury risk, especially during treatment initiation

• Diabetic retinopathy complications have been associated with rapid glucose improvement (particularly with semaglutide)

• Hypoglycaemia risk when combined with insulin or sulphonylureas

According to UK product information, GLP-1 receptor agonists are not recommended during pregnancy or breastfeeding when used for weight management. Those used for diabetes require individual benefit-risk assessment in pregnancy.

Regarding drug interactions, UK SmPCs indicate few clinically significant pharmacokinetic interactions. However, the delayed gastric emptying effect may affect the absorption of some oral medications, which may need to be considered for certain drugs with narrow therapeutic windows.

Cost-effectiveness represents another consideration. GLP-1 receptor agonists are expensive medications, and without robust efficacy data for addiction treatment, their use for this indication cannot be justified from a health economics perspective. NHS resources must be allocated based on evidence-based interventions with demonstrated clinical and cost-effectiveness.

What This Means for Patients: Practical Guidance

If you are struggling with addiction or substance use concerns, it is essential to understand that GLP-1 receptor agonists are not currently recommended or licensed treatments for addiction in the UK. Evidence-based treatments remain the appropriate first-line approach.

If you are experiencing problems with alcohol or substance use, you should:

• Contact your GP to discuss your concerns in a confidential, non-judgemental setting

• Access specialist addiction services through NHS referral pathways or organisations such as Turning Point, We Are With You, or Alcoholics Anonymous

• Consider evidence-based treatments including cognitive behavioural therapy, motivational interviewing, and where appropriate, licensed pharmacotherapies

• Visit NHS support pages for alcohol support (www.nhs.uk/live-well/alcohol-advice/alcohol-support) or drug addiction help (www.nhs.uk/live-well/addiction-support/drug-addiction-getting-help)

• Contact FRANK (www.talktofrank.com) for confidential drug information and advice

If you are already taking a GLP-1 receptor agonist for diabetes or weight management and notice changes in your substance use patterns:

• Inform your prescribing clinician about any changes you observe

• Do not alter your medication regimen without medical supervision

• Continue with your prescribed treatment plan for your licensed indication

• Seek appropriate addiction support through established pathways if needed

Important safety advice:

• Never obtain GLP-1 medications from unregulated sources or online pharmacies without proper medical oversight

• These medications require careful dose titration and monitoring for adverse effects

• Self-medication for addiction is potentially dangerous and may delay access to effective treatments

• Report any suspected side effects to the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk)

When to seek medical attention:

• Call 999 for life-threatening symptoms

• Contact NHS 111 for urgent medical advice when your GP is unavailable

• Seek immediate medical help for severe, persistent abdominal pain (potential pancreatitis)

• Signs of allergic reaction (rash, difficulty breathing, facial swelling)

• Symptoms of severe hypoglycaemia if taking other diabetes medications

• Any concerning symptoms or medication side effects

Whilst research into GLP-1 receptor agonists and addiction continues, patients deserve access to proven, evidence-based treatments. Speak with your healthcare provider about the most appropriate support for your individual circumstances.

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