GLP-1 receptor agonists present promise in treating substance use issues

A scientific evaluation 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.

Assessment: 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 evaluation revealed within the journal Drug and Alcohol Dependence offers an in depth evaluation of the findings of accessible medical 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 folks 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 persons are affected by cocaine use dysfunction and alcohol use dysfunction, respectively. The mortality fee related to cocaine overdose can be growing quickly worldwide, exceeding opioid overdose-related deaths.

In line 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 damage. Just like alcohol, tobacco smoking is one other main explanation for untimely loss of life.

All forms of substance addictions are clinically codified as substance use dysfunction, which is taken into account a persistent 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 medicine sometimes used to take care of glucose homeostasis in kind 2 diabetes sufferers. These agonists additionally play a significant position in nerve cell differentiation and inhibition of neuroinflammation. Moreover neuroprotective results, GLP-1 receptor agonists have been discovered to be concerned in mind networks related to reward and dependancy.

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

Systematic evaluation design

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

Moreover 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 evaluation of 39 research, the authors included 5 randomized managed medical trials within the ultimate evaluation. These trials included a complete of 630 individuals and used exenatide or dulaglutide as GLP-1 receptor agonists. The length of trials ranged from 6 to 26 weeks. Importantly, these trials exhibited a excessive diploma of heterogeneity when it comes to the forms of substances studied, affected person traits, and therapy protocols, which posed vital challenges to drawing definitive conclusions. General, the chosen trials had a low to reasonable danger of bias.

Essential observations

All 5 medical trials that have 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 lowering alcohol use dysfunction and nicotine use dysfunction. Importantly, these trials exhibited a excessive diploma of heterogeneity when it comes to the forms of substances studied, affected person traits, and therapy protocols, which posed vital challenges to drawing definitive conclusions.

Moreover, within the trial analyzing 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, corresponding to BMI, would possibly affect therapy outcomes.

Concerning 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 individuals.

Significance

This systematic evaluation highlights the potential therapeutic affect of GLP-1 receptor agonists in lowering substance use issues in grownup sufferers. Nonetheless, the authors urge warning in decoding these findings as a result of restricted variety of trials, the variations in examine designs, and the heterogeneity in affected person populations and substance varieties 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 alerts, which transform 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 methods, which consequence from behaviors much like dependancy to fats and sugar-rich meals.

Contemplating the widespread expression of GLP-1 receptors within the mind, the authors suggest that future research ought to concentrate on 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 more than likely to profit from these remedies.

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

The medical trials included within the evaluation had a excessive diploma of heterogeneity when it comes to substance varieties, sufferers’ traits, and kinds and doses of the administered GLP-1 receptor agonists. This variability restricted the potential of conducting a meta-analysis and emphasised the necessity for standardized protocols in future analysis.

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