A major new study suggests that blockbuster GLP-1 drugs, which have already transformed the treatment of diabetes and obesity, may also help prevent addiction to various substances and reduce severe related consequences. An analysis published Wednesday in a medical journal examined the electronic health records of over 600,000 diabetic patients from the U.S. Department of Veterans Affairs (VA). The study found that patients treated with drugs like Ozempic and Mounjaro were less likely to develop addictions to substances such as alcohol, nicotine, cocaine, and opioids compared to patients using another class of diabetes medications. The research also indicated that among individuals already struggling with addiction, the use of GLP-1 medications was associated with a reduced risk of hospitalization, drug overdose, and death. These latest findings suggest—though not yet proven directly—that these weight-loss drugs might act on the fundamental source of "craving," which affects over 48 million Americans with substance use disorders. "The medications are essentially tackling the root causes behind multiple addictions," said the study's lead author, Ziyad Al-Aly, chief of research at the VA St. Louis Health Care System. Key aspects of the study, published in *The BMJ*, are outlined below: Previous research has indicated that drugs known as GLP-1 receptor agonists may reduce addictive behaviors by acting on the brain's reward pathways. However, earlier studies were smaller and typically focused on a single substance. In one of the largest studies of its kind to date, Al-Aly and his team analyzed three years of electronic health data from over 600,000 diabetic VA patients, comparing those using GLP-1 drugs with those using other anti-diabetic medications. The researchers divided patients into seven parallel trials, analyzing the risk of addiction to various substances including alcohol, cannabis, cocaine, nicotine, and opioids. An additional trial examined the risk of specific harms in people with existing addictions who were taking different medications. The results showed that individuals starting GLP-1 medication had a lower risk of developing addiction to multiple substances. Compared to other medications, GLP-1 users experienced the following reductions in addiction risk: - Alcohol: 18% decrease - Cannabis: 14% decrease - Cocaine: 20% decrease - Nicotine: 20% decrease - Opioids: 25% decrease Among patients already diagnosed with a substance use disorder, using GLP-1 drugs was also associated with reduced risks: - 31% lower risk of emergency department visits - 26% lower risk of hospitalization - 25% lower risk of suicidal thoughts or attempts - 39% lower risk of drug overdose - 50% lower risk of death Overall, over three years, approximately 7 cases of substance use disorder and 12 serious harm events could be prevented per 1,000 users, Al-Aly stated. The study has some limitations. The data came from the Veterans Health Administration, which primarily serves an older, white, male population. However, Al-Aly noted that results were largely consistent among the more than 35,000 women included. Additionally, the study only included data from diabetic patients, not the general population. Researchers could not control for all factors that might influence the results, such as socioeconomic status or lifestyle choices. Furthermore, the study compared GLP-1 drugs against another medication, not against no treatment at all. As an observational study, the analysis can only show an association between GLP-1 drug use and reduced addiction risk; it cannot prove the drugs directly cause the reduction. The findings are "highly striking," said Lorenzo Leggio, clinical director at the National Institute on Drug Abuse, who was not involved in the research. "Although we don't yet fully understand the mechanism, the GLP-1 system appears to be influencing the biological underpinnings of addiction and the core mechanisms behind all these disorders," he said. Clinical trials for diabetes and weight loss have shown that GLP-1 drugs act on hormones in the gut and brain to control appetite and satiety, reducing so-called "food noise" (persistent intrusive thoughts about food). Leggio suggested the same mechanism might also reduce "alcohol or drug noise." Growing evidence that GLP-1 drugs might prevent substance use disorders is exciting, said Anna Lembke, an addiction medicine expert at Stanford University. "From a pharmacotherapy perspective, it's been a long time since we've had a new tool for treating addiction," she noted, adding that some addiction specialists have already begun using GLP-1 drugs off-label, particularly when other treatments have failed. She cautioned, however, that GLP-1 drugs are not equally effective for all patients and carry certain risks that must be weighed against potential benefits. Al-Aly emphasized that this study alone is insufficient to support using GLP-1 drugs for preventing or treating substance use disorders. Randomized controlled clinical trials—directly comparing the drug against a placebo—are needed to draw such conclusions. Leggio pointed out that several related clinical trials are currently underway. Researchers are seeking new addiction treatments because addiction is a major cause of global disease and death. "The chronic disease consequences of these addictive substances are actually enormous in our society," Leggio said.