How GLP-1 agonists may remodel dependancy therapy

It’s truthful to say that most individuals are in all probability acquainted by now with GLP-1 medication and their revolutionary capacity to deal with diabetes and weight problems. However the hype round this class of medicine isn’t just restricted to those indications. Final 12 months, the U.S. Meals and Drug Administration (FDA) permitted Novo Nordisk’s blockbuster drug Wegovy to cut back the danger of significant coronary heart issues in overweight or chubby adults. And now, researchers are exploring the potential of GLP-1 medication for treating dependancy – an space of investigation that at the moment seems to be gaining some momentum. 

How can GLP-1 medication deal with dependancy? 

It’d sound unusual at first {that a} diabetes and weight reduction drug has the potential to deal with dependancy problems, however observations from researchers have led to rising knowledge, anecdotal studies, and pharmacoepidemiologic findings that recommend GLP-1 medication may very well be efficient for dependancy by lowering drug use and craving via the modulation of reward pathways, stress responses, and cognitive capabilities. 

Though the exact mechanisms by which GLP-1 medication regulate dependancy stay unclear, it’s thought that they act in an analogous solution to how they deal with weight problems, the place they act on reward facilities of the mind to cut back urge for food. Two mind areas which have GLP-1 receptors current are the ventral tegmental space and nucleus accumbens, which occur to be crucial within the improvement of substance use problems, the place addictive substances hijack pure reward pathways, resulting in compulsive behaviors. On this case, it’s believed that GLP-1 agonists act on the receptors in these areas to suppress dependancy. 

A lot of the analysis on this space has targeted particularly on alcohol dependancy, and researchers have recognized for some time now from animal research that GLP-1 receptor agonists lower alcohol consumption, cut back the motivation to eat alcohol, and even stop relapse consuming by probably reducing alcohol-induced reward.

Extra lately, the consequences of GLP-1 medication on dependancy have been studied in people, with outcomes up to now wanting very promising certainly. 

Research recommend blockbuster GLP-1 medication can deal with alcohol dependancy

In November 2024, a examine printed in JAMA Psychiatry made the headlines because it advised that the blockbuster medication Ozempic and Wegovy may probably be repurposed to assist folks with alcohol use dysfunction. 

This examine, primarily based in Sweden, appeared on the medical information of 227,868 folks with an official prognosis of alcohol use dysfunction between 2006 and 2021. Amongst this affected person inhabitants, 4,321 folks took semaglutide – the lively ingredient in Ozempic and Wegovy – and a couple of,509 used liraglutide, an older GLP-1 drug. The researchers concluded that individuals utilizing these medication have been much less more likely to be hospitalized for issues linked to alcohol use dysfunction than sufferers who didn’t take the medication. 

To place it into perspective, the usage of semaglutide was related to a 36% decrease danger of hospitalization and liraglutide was related to a 28% decrease danger. Comparatively, the usage of naltrexone, a drug already permitted to deal with opioid and alcohol use dysfunction, was related to solely a 14% discount within the danger of hospitalization. 

The “markedly diminished danger” right here for alcohol use dysfunction sufferers taking GLP-1 agonists means that this class of medicine would possibly really be more practical than the present crop of formally permitted medicines for treating alcohol dependancy. 

The info from this examine follows on from a number of others which have been carried out on the consequences of GLP-1 medication on alcohol consumption. A scientific trial printed in 2022 discovered that an older GLP-1 drug referred to as exenatide additionally diminished consuming amongst those that had each alcohol use dysfunction and weight problems. In the meantime, a number of different research have examined consuming habits amongst folks taking GLP-1 medication who would not have alcohol use dysfunction. 

Though most research on this subject depend on affected person information, a small managed scientific trial reported final month supplied additional proof that GLP-1 agonists could assist deal with alcohol dependancy. On this part 2 examine, 48 sufferers with weight problems or who have been chubby and in addition had alcohol use dysfunction have been randomly assigned both a placebo or a low dose of semaglutide, with researchers testing how a lot the drug modified consuming habits after about two months.

Utilizing a take a look at wherein trial volunteers have been provided their most well-liked beverage to drink over two hours, the examine discovered that individuals who acquired semaglutide drank about 50% lower than the folks given placebo on the finish of the eight-week therapy interval, as measured by breath alcohol focus and grams of alcohol consumed. 

Though the trial will not be a conclusive verdict on semaglutide’s efficacy for dependancy as a result of small affected person pool, and the outcomes are far in need of what can be wanted for the FDA to formally approve the GLP-1 drug’s use in alcohol use dysfunction, it does present encouragement for firms who’re pondering of testing their medication within the indication within the not-so-distant future. 

And it isn’t simply alcohol dependancy the place GLP-1 medication have been discovered to have a constructive impact. One other observational trial printed in September 2024 discovered that semaglutide was related to diminished opioid overdose danger in sufferers with comorbid sort 2 diabetes and opioid use dysfunction, and a examine printed in July final 12 months additionally discovered that semaglutide was related to a decrease danger of normal tobacco use in sufferers with sort 2 diabetes who have been tobacco people who smoke, with semaglutide-treated sufferers in search of fewer healthcare assets to deal with their tobacco dependancy.

Novo Nordisk and Eli Lilly flip their consideration to GLP-1 results on alcohol

Because the potential of GLP-1 agonists for dependancy positive aspects traction, massive pharma can be beginning to take discover, specifically the 2 pharma giants which might be chargeable for the event of the present crop of blockbuster GLP-1 medication: Novo Nordisk and Eli Lilly.

Novo is at the moment finishing up a part 2 trial testing semaglutide – together with two different medication – for the therapy of alcoholic liver illness. Though the first endpoint right here is the therapy of liver injury, one of many trial’s secondary endpoints is alcohol consumption. 

The corporate has but to announce any important knowledge from this examine, which solely started in Might final 12 months, with an estimated completion date of January 2026. 

It is usually price noting that final week, Novo’s head of improvement, Martin Holst Lange, signaled in a media name the corporate’s intent to analyze particularly whether or not semaglutide might help sufferers cut back drug or alcohol abuse. “We’ll additional look into this and discover how we might help sufferers with dependancy, probably with GLP-1,” Lange stated, additionally including that “it must be addressed in a scientific, and clearly additionally from a regulatory perspective, very rigorous manner so we are able to actually see the potential influence of GLP-1 in that area.” 

Nonetheless, in response to questions from Biospace, a Novo spokesperson stated that Lange was referring to the already ongoing work finding out semaglutide on liver injury and alcohol use in its part 2 trial, and that the corporate has no plans to review the drug in broader dependancy indications. Whether or not there’s something extra behind this, we must wait and see. 

Eli Lilly, in the meantime, has clearly expressed plans to check GLP-1 medication for dependancy. It had been contemplating this feature for a minimum of a 12 months and a half earlier than chief govt officer (CEO) David Ricks stated in December that the corporate will start giant research in alcohol and drug abuse in 2025, trying to validate current analysis that implies a possible profit on this space. 

We’ll probably hear extra about Eli Lilly’s plans within the coming months. 

GLP-1 medication may fill the hole in dependancy therapy

Up to now, a number of systemic critiques have been carried out to supply a complete evaluation of scientific trials to find out the influence of GLP-1 receptor agonists in lowering substance use dysfunction in sufferers. Though nearly all of these critiques present constructive knowledge for the potential of GLP-1 medication for dependancy, the findings are considerably inconclusive as a result of examine variability and affected person variations, demonstrating that extra targeted scientific research with dependancy as a main endpoint are wanted.

Certainly, Eli Lilly’s senior vp (SVP) of neurodegeneration analysis, Andrew Adams, stated in June 2023 that the corporate was carefully monitoring the updates from sufferers associated to dependancy, however cautioned that human research can be troublesome to run provided that they usually have excessive variability ensuing from self-reported outcomes.  

Even when wanting on the aforementioned Swedish examine, utilizing hospitalization to find out the medication’ results on alcohol use dysfunction can be thought-about an imperfect measure. 

However, specialists stated it’s a good place to begin. And based on Alex DiFeliceantonio, an assistant professor at Virginia Tech’s Fralin Biomedical Analysis Institute, in an interview with NBC Information, with hospital knowledge extensively obtainable, it may possibly assist researchers decide which medication may go for several types of dependancy and which scientific trials they need to run first.

One other potential query that scientific trials might want to assess is whether or not GLP-1 medication are literally protected to take for folks with out weight problems or diabetes, as the load loss these medication induce may very well be a harmful aspect impact.

As extra trials proceed to happen testing GLP-1 medication for the therapy of different indications, together with coronary heart failure, sleep apnea, superior fatty liver illness, and cardiovascular occasions, extra data is more likely to come to gentle in regards to the potential of those medication, which, proper now, appears to be infinite. 

Actually, relating to dependancy, if GLP-1 agonists are discovered to have an impact, it could be a major breakthrough for sufferers; the one medicines at the moment permitted for treating addictions are likely to purpose at lowering withdrawal signs for sufferers quitting opioid medication, comparable to methadone and buprenorphine, but nothing is out there up to now that truly reduces cravings for alcohol or medication.