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

A scientific overview reveals that GLP-1 receptor agonists might assist scale back sure substance use issues, however findings are inconsistent resulting from examine variability and affected person variations.

Evaluate: 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 overview revealed within the journal Drug and Alcohol Dependence supplies an in depth evaluation of the findings of obtainable 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% improve in its prevalence has been noticed in 2021 in comparison with that noticed over the previous ten years.

Latest estimates point out that about 5 million and 280 million persons are affected by cocaine use dysfunction and alcohol use dysfunction, respectively. The mortality charge related to cocaine overdose can also be growing 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 damage. Just like alcohol, tobacco smoking is one other main reason for untimely demise.

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 medication sometimes used to keep up glucose homeostasis in sort 2 diabetes sufferers. These agonists additionally play a significant function 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 habit.

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

Systematic overview design

The authors screened numerous digital databases to establish 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 influence 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 overview of 39 research, the authors included 5 randomized managed medical trials within the closing evaluation. These trials included a complete of 630 contributors 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. General, the chosen trials had a low to average danger of bias.

Vital observations

All 5 medical 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 influence of GLP-1 receptor agonist in lowering 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 analyzing alcohol use dysfunction, a major discount in alcohol consumption was noticed solely in a selected subgroup of sufferers with weight problems, suggesting that affected person traits, reminiscent of BMI, may 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 contributors.

Significance

This systematic overview highlights the potential therapeutic influence 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 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 just 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 habit within the mind programs, which outcome from behaviors just like habit 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 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 particular affected person subtypes who’re probably to profit from these remedies.

In addition they spotlight the necessity for future medical trials to extra conclusively decide the dose and period 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 overview 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 overview needs to be seen with some warning with respect to the potential therapeutic impact of GLP-1 receptor agonists on substance use dysfunction.