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The list of health conditions that benefit from the GLP-1 weight loss and diabetes drugs like Ozempic, Wegovy, Mounjaro and Zepbound, continues to grow.
The drugs are already approved to lower the risk of heart disease, sleep apnea, kidney and liver conditions. In the latest study on the medications, published in the BMJ, researchers led by Dr. Ziyad Al-Aly, from the department of medicine at the Washington University School of Medicine, report that people taking the drugs lowered their risk of developing addictions, as well as reduced the negative consequences of addictive behaviors, including hospitalizations, overdose and death.
“There are a smattering of studies here and there, small studies that look at one type of substance use—for example, alcohol—but there really is not a single human study that comprehensively evaluates two things: 1) the risk of new onset substance use disorders across all major substances, and 2) harm reduction, or the question of do these drugs really reduce the risk of drug overdoses, drug deaths, drug-related hospitalizations, emergency room visits, and suicides,” says Al-Aly.
He and his team analyzed health records from more than 600,000 people in the Department of Veterans Affairs system, who represented a broad swath of the population, although most were men. All of the participants were diagnosed with diabetes and prescribed either a GLP-1 drug like Ozempic or Mounjaro, or a different group of diabetes medications known as SGLT2 inhibitors, such as Farxiga or Jardiance. While GLP-1 drugs work in the brain, the SGLT2 drugs do not, acting instead on the kidneys to remove excess sugar. That’s why previous studies suggested that GLP-1 drugs could have benefits in treating addictions—as weight loss drugs, they suppress the reward signals in the brain, in the mesolimbic system, that reinforce cravings and so-called food noise that many people with obesity report. Addictive substances such as nicotine, alcohol, cocaine, and opioids tap into the same brain region to reinforce cravings for and dependence on those substances.
Among people who did not currently have a substance use disorder, Al-Aly studied their likelihood of becoming addicted to alcohol, cannabis, cocaine, nicotine, or opioids over a three year follow-up period after being prescribed either a GLP-1 or a SGLT2 inhibitor. Across each of the different substances, people taking the GLP-1 showed anywhere from 14% to 25% reduced risk of developing an addiction to one of them, compared to people prescribed an SGLT2 inhibitor. The reduction was greatest for the chance of developing a dependence on opioids, which could be an important new strategy for addressing the growing epidemic of opioid addiction around the world.
The researchers then looked at whether the weight loss drugs had any benefit in helping people who already had a substance use disorder. And they found that GLP-1 medications were helpful in lowering the risk of emergency department visits by 29%, hospitalizations due to their addiction by 26%, overdose by 39%, and deaths from drug-related causes by 50%.
“The biggest revelation for me is that [these GLP-1 drugs] are working across different substances,” says Al-Aly. “Previously, in addiction medicine, there were medications tailored to treat specific substances—nicotine patches for smoking, other treatments for alcohol and another treatment for opioids. There is no medicine, or no precedent in our armamentarium that actually has this property of working across addictive substances.”
This means the results could provide a key foundation for establishing GLP-1 medications as a potentially new class of drugs that could both prevent and treat different types of addictions, he says. But more studies need to be conducted to better understand exactly how the medications should be used in these cases. The current study, for instance, does not delve into the issue of dose or duration of the medications—studies in weight loss show that once people stop taking the drugs, their effects dissipate and many people regain weight. The same phenomenon could occur in addictions, since the drugs work by suppressing the reward signals in the brain; if the drugs are no longer present, those craving signals could return.
“I worry about what will happen since if [these drugs] put the lid on craving in the mesolimbic system [of the brain], then all of a sudden people stop taking them, that the craving then comes back with a vengeance,” says Al-Aly. “I worry that in dealing with people with cravings, and people at risk of overdosing and other problems, that we need to understand and appreciate the uncertainties here more.”
He says that another issue that must be explored further before prescribing GLP-1s to prevent or treat addictions is the ability of the brain to adapt. If people start taking GLP-1s to prevent or control addictions, it’s not clear whether the brain would develop a tolerance to the drugs and therefore reach a point at which the medications would no longer effectively control cravings. “I’m excited by these results,” says Al-Aly. “But as a scientist, I would not advise prescribing [GLP-1s] for the sole indication of addiction at this point, pending more studies and understanding, and more resolution of uncertainties.”
Still, the data are the first step in understanding a potentially powerful new way these medications could be used to address another significant health issue that so far hasn’t enjoyed truly effective prevention and treatment strategies. If the current data are replicated and better understood, for example, it could open the door to preventing addictions before they become harmful and cause irreparable harm, both physically and behaviorally. Such an intervention would be unprecedented in the addiction space, and require additional research to identify stronger risk factors for addictive behaviors, whether they are genetic, environmental, or behavioral, or a combination.
“Who benefits from them the most is the next big question,” says Al-Aly. “At this point, we don’t really know. Are there subsets of people among these 600,000 person cohort who might benefit more from GLP-1s? We would need additional follow up studies.”
For now, even if the data don’t support using the GLP-1 medications to just prevent or treat addictions, Al-Aly says that if people qualify for the drugs because they have diabetes or are overweight or obese, and they also want to quit smoking, stop drinking, or control their opioid dependence, then the GLP-1 medications could help. “For those people, these data give them an additional rationale,” he says. “It will literally help them reach their two goals. But for prescribing for the sole purpose of controlling addiction—I don’t think we are there yet, and need to resolve more uncertainties about what happens when people discontinue the medications, as well as neuroadaptation, before we start making recommendations.”
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