Can GLP-1 agonists help treat addiction?

Newsletter Signup - Under Article / In Page"*" indicates required fieldsSubscribe to our newsletter to get the latest biotech news!By clicking this I agree to receive Labiotech's newsletter and understand that my personal data will be processed according to the Privacy Policy.*Business email* NameThis field is for validation purposes and should be left unchanged. It is fair to say that most people are probably familiar by now with GLP-1 drugs and their revolutionary ability to treat diabetes and obesity. But the hype around this class of drugs is not just limited to these indications. Last year, the U.S. Food and Drug Administration (FDA) approved Novo Nordisk’s blockbuster drug Wegovy to reduce the risk of serious heart problems in obese or overweight adults. And now, researchers are exploring the potential of GLP-1 drugs for treating addiction – an area of investigation that currently looks to be gaining some momentum. Table of contentsHow can GLP-1 drugs treat addiction? It might sound strange at first that a diabetes and weight loss drug has the potential to treat addiction disorders, but observations from researchers have led to emerging data, anecdotal reports, and pharmacoepidemiologic findings that suggest GLP-1 drugs could be effective for addiction by reducing drug use and craving through the modulation of reward pathways, stress responses, and cognitive functions. Although the precise mechanisms by which GLP-1 drugs regulate addiction remain unclear, it is thought that they act in a similar way to how they treat obesity, where they act on reward centers of the brain to reduce appetite. Two brain regions that have GLP-1 receptors present are the ventral tegmental area and nucleus accumbens, which happen to be critical in the development of substance use disorders, where addictive substances hijack natural reward pathways, leading to compulsive behaviors. In this case, it is believed that GLP-1 agonists act on the receptors in these regions to suppress addiction. Most of the research in this area has focused specifically on alcohol addiction, and researchers have known for a while now from animal studies that GLP-1 receptor agonists decrease alcohol intake, reduce the motivation to consume alcohol, and even prevent relapse drinking by potentially lowering alcohol-induced reward.More recently, the effects of GLP-1 drugs on addiction have been studied in humans, with results so far looking very promising indeed. Studies suggest blockbuster GLP-1 drugs can treat alcohol addictionIn November 2024, a study published in JAMA Psychiatry made the headlines as it suggested that the blockbuster drugs Ozempic and Wegovy could potentially be repurposed to help people with alcohol use disorder. This study, based in Sweden, looked at the medical records of 227,868 people with an official diagnosis of alcohol use disorder between 2006 and 2021. Among this patient population, 4,321 people took semaglutide – the active ingredient in Ozempic and Wegovy – and 2,509 used liraglutide, an older GLP-1 drug. The researchers concluded that people using these drugs were less likely to be hospitalized for problems linked to alcohol use disorder than patients who did not take the drugs. To put it into perspective, the use of semaglutide was associated with a 36% lower risk of hospitalization and liraglutide was associated with a 28% lower risk. Comparatively, the use of naltrexone, a drug already approved to treat opioid and alcohol use disorder, was associated with only a 14% reduction in the risk of hospitalization. Suggested Articles GLP-1 agonists: what’s the hype about? Can GLP-1 agonists, the miraculous obesity drugs, treat cardiovascular diseases? New non-opioid pain medication: How is the biotech industry fighting pain after the opioid crisis? GLP-1 shortage: Can biotech companies keep up with rising demand? Obesity drug success sparks biotech buying spree The “markedly reduced risk” here for alcohol use disorder patients taking GLP-1 agonists suggests that this class of drugs might actually be more effective than the current crop of officially approved medications for treating alcohol addiction. The data from this study follows on from several others that have been conducted on the effects of GLP-1 drugs on alcohol consumption. A clinical trial published in 2022 found that an older GLP-1 drug called exenatide also reduced drinking among those who had both alcohol use disorder and obesity. Meanwhile, several other studies have examined drinking habits among people taking GLP-1 drugs who do not have alcohol use disorder. Although most studies on this topic rely on patient records, a small controlled clinical trial reported last month provided further evidence that GLP-1 agonists may help treat alcohol addiction. In this phase 2 study, 48 patients with obesity or who were overweight and also had alcohol use disorder were randomly assigned either a placebo or a low dose of semaglutide, with researchers testing how much the drug changed drinking habits after about two months.Using a test in which trial volunteers were offered their preferred beverage to drink over two hours, the study found that people who received semaglutide drank about 50% less than the people given placebo at the end of the eight-week treatment period, as measured by breath alcohol concentration and grams of alcohol consumed. Although the trial is not a conclusive verdict on semaglutide’s efficacy for addiction due to the small patient pool, and the results are far short of what would be needed for the FDA to formally approve the GLP-1 drug’s use in alcohol use disorder, it does provide encouragement for companies who are thinking of testing their drugs in the indication in the not-so-distant future. And it is not just alcohol addiction where GLP-1 drugs have been found to have a positive effect. Another observational trial published in September 2024 found that semaglutide was associated with reduced opioid overdose risk in patients with comorbid type 2 diabetes and opioid use disorder, and a study published in July last year also found that semaglutide was associated with a lower risk of regular tobacco use in patients with type 2 diabetes who were tobacco smokers, with semaglutide-treated patients seeking fewer healthcare resources to treat their tobacco addiction.Novo Nordisk and Eli Lilly turn their attention to GLP-1 effects on alcoholAs the potential of GLP-1 agonists for addiction gains traction, big pharma is also starting to take notice, namely the two pharma giants that are responsible for the development of the current crop of blockbuster GLP-1 drugs: Novo Nordisk and Eli Lilly.Novo is currently carrying out a phase 2 trial testing semaglutide – along with two other drugs – for the treatment of alcoholic liver disease. Although the primary endpoint here is the treatment of liver damage, one of the trial’s secondary endpoints is alcohol consumption. The company has yet to announce any significant data from this study, which only began in May last year, with an estimated completion date of January 2026. It is also worth noting that last week, Novo’s head of development, Martin Holst Lange, signaled in a media call the company’s intent to investigate specifically whether semaglutide can help patients reduce drug or alcohol abuse. “We will further look into this and explore how we can help patients with addiction, potentially with GLP-1,” Lange said, also adding that “it has to be addressed in a scientific, and obviously also from a regulatory perspective, very rigorous way so we can really see the potential impact of GLP-1 in that space.” However, in response to questions from Biospace, a Novo spokesperson said that Lange was referring to the already ongoing work studying semaglutide on liver damage and alcohol use in its phase 2 trial, and that the company has no plans to study the drug in broader addiction indications. Whether there is anything more behind this, we will have to wait and see. Eli Lilly, meanwhile, has clearly expressed plans to test GLP-1 drugs for addiction. It had been considering this option for at least a year and a half before chief executive officer (CEO) David Ricks said in December that the company will begin large studies in alcohol and drug abuse in 2025, looking to validate existing research that suggests a potential benefit in this area. We will potentially hear more about Eli Lilly’s plans in the coming months. GLP-1 drugs could fill the gap in addiction treatmentSo far, multiple systemic reviews have been conducted to provide a comprehensive analysis of clinical trials to determine the impact of GLP-1 receptor agonists in reducing substance use disorder in patients. Although the majority of these reviews show positive data for the potential of GLP-1 drugs for addiction, the findings are somewhat inconclusive due to study variability and patient differences, demonstrating that more focused clinical studies with addiction as a primary endpoint are needed.Indeed, Eli Lilly’s senior vice president (SVP) of neurodegeneration research, Andrew Adams, said in June 2023 that the company was closely monitoring the updates from patients related to addiction, but cautioned that human studies would be difficult to run given that they often have high variability resulting from self-reported outcomes.  Even when looking at the aforementioned Swedish study, using hospitalization to determine the drugs’ effects on alcohol use disorder is also considered an imperfect measure. Nevertheless, experts said it is a good place to start. And according to Alex DiFeliceantonio, an assistant professor at Virginia Tech’s Fralin Biomedical Research Institute, in an interview with NBC News, with hospital data widely available, it can help researchers determine which drugs may work for different types of addiction and which clinical trials they should run first.Another potential question that clinical trials will need to assess is whether GLP-1 drugs are actually safe to take for people without obesity or diabetes, as the weight loss these drugs induce could be a damaging side effect.As more trials continue to take place testing GLP-1 drugs for the treatment of other indications, including heart failure, sleep apnea, advanced fatty liver disease, and cardiovascular events, more information is likely to come to light about the potential of these drugs, which, right now, seems to be endless. Certainly, when it comes to addiction, if GLP-1 agonists are found to have an effect, it would be a significant breakthrough for patients; the only medications currently approved for treating addictions tend to aim at reducing withdrawal symptoms for patients quitting opioid drugs, such as methadone and buprenorphine, yet nothing is available so far that actually reduces cravings for alcohol or drugs. 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