GLP-1 receptor agonists show promise in treating substance use disorders

A scientific assessment reveals that GLP-1 receptor agonists could assist scale back sure substance use issues, however findings are inconsistent as a consequence of examine variability and affected person variations.

Evaluation: POTENTIAL ROLE OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS IN SUBSTANCE USE DISORDER: A SYSTEMATIC REVIEW OF RANDOMIZED TRIALS. Picture Credit score: Designua / Shutterstock

A scientific assessment revealed within the journal Drug and Alcohol Dependence gives an in depth evaluation of the findings of accessible scientific trials that investigated the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on substance use dysfunction.

Background

Substance use dysfunction is a number one public well being concern, affecting roughly 40 million individuals worldwide. A 23% enhance in its prevalence has been noticed in 2021 in comparison with that noticed over the previous ten years.

Current estimates point out that about 5 million and 280 million individuals are affected by cocaine use dysfunction and alcohol use dysfunction, respectively. The mortality price related to cocaine overdose can be rising quickly worldwide, exceeding opioid overdose-related deaths.

In accordance with the World Well being Group (WHO), alcohol use dysfunction is related to 5.3% of deaths and 5.1% of the worldwide burden of illness and harm. Much like alcohol, tobacco smoking is one other main reason behind untimely loss of life.

All forms of substance addictions are clinically codified as substance use dysfunction, which is taken into account a power illness characterised by a transition from leisure drug use to compulsive and disordered use.

Glucagon-like peptide-1 (GLP-1) receptor agonists are a category of medication usually used to keep up glucose homeostasis in kind 2 diabetes sufferers. These agonists additionally play a significant function in nerve cell differentiation and inhibition of neuroinflammation. In addition to neuroprotective results, GLP-1 receptor agonists have been discovered to be concerned in mind networks related to reward and dependancy.

On this systematic assessment, the authors carried out a complete evaluation of scientific trials to find out the affect of GLP-1 receptor agonists in decreasing substance use dysfunction in sufferers.

Systematic assessment design

The authors screened varied digital databases to determine scientific trials that investigated the impact of GLP-1 receptor agonists on various kinds of substance use issues (alcohol, nicotine, and cocaine use issues) in grownup sufferers.

In addition to protecting results on substance use issues, the authors analyzed the affect of GLP-1 receptor agonists on physique weight administration, physique mass index (BMI), and glycated hemoglobin degree (a measure of glycemic management).

After a full-text assessment of 39 research, the authors included 5 randomized managed scientific trials within the ultimate evaluation. These trials included a complete of 630 members and used exenatide or dulaglutide as GLP-1 receptor agonists. The period of trials ranged from 6 to 26 weeks. Importantly, these trials exhibited a excessive diploma of heterogeneity by way of the forms of substances studied, affected person traits, and therapy protocols, which posed important challenges to drawing definitive conclusions. Total, the chosen trials had a low to reasonable danger of bias.

Vital observations

All 5 scientific trials that had been included within the evaluation reported GLP-1 receptor agonist-mediated discount in substance use dysfunction, with two trials respectively reporting a major therapeutic affect of GLP-1 receptor agonist in decreasing alcohol use dysfunction and nicotine use dysfunction. Importantly, these trials exhibited a excessive diploma of heterogeneity by way of the forms of substances studied, affected person traits, and therapy protocols, which posed important challenges to drawing definitive conclusions.

Moreover, within the trial inspecting alcohol use dysfunction, a major discount in alcohol consumption was noticed solely in a particular subgroup of sufferers with weight problems, suggesting that affected person traits, akin to BMI, would possibly affect therapy outcomes.

Relating to secondary outcomes, 4 out of 5 chosen trials reported a major discount in physique weight, BMI, and glycated hemoglobin ranges in GLP-1 receptor agonist-treated members.

Significance

This systematic assessment highlights the potential therapeutic affect of GLP-1 receptor agonists in decreasing substance use issues in grownup sufferers. Nevertheless, the authors urge warning in decoding these findings because of the restricted variety of trials, the variations in examine designs, and the heterogeneity in affected person populations and substance sorts studied.

The affiliation between weight problems and substance use dysfunction has broadly been documented within the literature. It has been noticed that publicity to extremely palatable meals will increase key neuroendocrine indicators, which rework mind reward circuits to bolster pathological consuming behaviors.

This phenomenon is much like that that occurs on the neurobiological degree with substance use dysfunction. Research utilizing animal fashions of weight problems have discovered typical neurobiological traits of dependancy within the mind programs, which end result from behaviors much like dependancy to fats and sugar-rich meals.

Contemplating the widespread expression of GLP-1 receptors within the mind, the authors advocate that future research ought to give attention to figuring out the important thing neurocircuits concerned in mediating the consequences of GLP-1 receptor agonists on substance use dysfunction, in addition to decide the precise affected person subtypes who’re most definitely to profit from these remedies.

In addition they spotlight the necessity for future scientific trials to extra conclusively decide the dose and period of GLP-1 receptor agonist-based remedies in sufferers hooked on various kinds of substances, together with amphetamines, opioids, and benzodiazepines.

The scientific trials included within the assessment had a excessive diploma of heterogeneity by way of substance sorts, sufferers’ traits, and kinds and doses of the administered GLP-1 receptor agonists. This variability restricted the potential for conducting a meta-analysis and emphasised the necessity for standardized protocols in future analysis.

As talked about by the authors, the findings of this assessment needs to be considered with some warning with respect to the potential therapeutic impact of GLP-1 receptor agonists on substance use dysfunction.