GLP-1 Weight-Loss Drugs Could Address a Range of Addictions

The list of health conditions that benefit from GLP-1 medications for weight loss and diabetes, such as Ozempic, Wegovy, Mounjaro, and Zepbound, continues to grow.

The drugs are already approved to reduce the risk of heart disease, sleep apnea, and kidney and liver disease. In the latest drug study, published in the BMJResearchers led by Dr. Ziyad Al-Aly, of the Department of Medicine at the University of Washington School of Medicine, report that people taking these drugs reduced their risk of developing addiction, as well as the negative consequences of addictive behaviors, including hospitalizations, overdoses and death.

“There are a handful of studies here and there, small studies that look at one type of substance use, for example alcohol, but there isn’t really a single human study that comprehensively assesses two things: 1) the risk of new substance use disorders for all major substances, and 2) harm reduction, or whether these drugs actually reduce the risk of drug overdoses, drug-related deaths, drug-related hospitalizations, drugs, emergency room visits and suicides,” says Al-Aly.

He and his team analyzed the medical records of more than 600,000 people in the Department of Veterans Affairs system, who represented a large portion of the population, although most were men. All participants were diagnosed with diabetes and prescribed either a GLP-1 drug like Ozempic or Mounjaro or another group of diabetes medications called SGLT2 inhibitors, such as Farxiga or Jardiance. While GLP-1 drugs work in the brain, SGLT2 drugs do not, instead working on the kidneys to remove excess sugar. That’s why previous studies suggested that GLP-1 drugs might have benefits in treating addictions: As weight-loss drugs, they suppress reward signals in the brain, in the mesolimbic system, that reinforce cravings and so-called food noise that many obese people report. Addictive substances such as nicotine, alcohol, cocaine, and opioids tap into the same region of the brain to reinforce cravings and dependence on these substances.

Among people who did not currently have substance use disorders, 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 a GLP-1 or SGLT2 inhibitor. For each of the different substances, people taking GLP-1 had a 14% to 25% reduced risk of developing dependence on one of them, compared to people who were prescribed an SGLT2 inhibitor. The largest reduction is in the risk of developing opioid addiction, which could be an important new strategy to combat the growing epidemic of opioid addiction worldwide.

The researchers then looked at whether weight loss medications could help people who already had a substance use disorder. And they found that GLP-1 drugs were helpful in reducing the risk of emergency room visits by 29%, hospitalizations due to addiction by 26%, overdoses by 39%, and deaths from drug-related causes by 50%.

“The biggest revelation for me is that [these GLP-1 drugs] work on different substances,” says Al-Aly. “Previously, in addiction medicine, there were medications designed to treat specific substances: nicotine patches for smoking, other treatments for alcohol, and another treatment for opioids. There is no drug, nor any precedent in our arsenal, which really has this property of acting against addictive substances.

This means the findings could provide a critical basis for establishing GLP-1 drugs as a potential new class of drugs that can both prevent and treat different types of addictions, he says. But more studies need to be done to better understand exactly how the drugs should be used in these cases. The current study, for example, does not address the question of dose or duration of medications: Weight loss studies show that once people stop taking the medications, their effects wear off and many people regain weight. The same phenomenon could occur in the case of addictions, since drugs work by suppressing reward signals in the brain; if the medications are no longer present, these withdrawal signals could return.

“I worry about what will happen because if [these drugs] put an end to lack of desire in the mesolimbic system [of the brain]”And then all of a sudden people stop taking them, and then the craving comes back with a vengeance,” says Al-Aly. “I worry that in dealing with people suffering from craving, and people at risk of overdose and other problems, we need to understand and appreciate more the uncertainties here.”

He says another issue that needs to be explored before prescribing GLP-1 to prevent or treat addictions is the brain’s ability to adapt. If people start taking GLP-1 to prevent or control addictions, it is unclear whether the brain will develop a tolerance to the drugs and therefore reach a point where the drugs will no longer effectively control cravings. “I am excited about these results,” says Al-Aly. “But as a scientist, I would not advise prescribing [GLP-1s] for the sole indication of dependence at this stage, pending further study and understanding, and further resolution of uncertainties.

Nonetheless, the data represent the first step in understanding a potentially powerful new way to use these drugs to address another important health problem that, until now, has not benefited from truly effective prevention and treatment strategies. If current data is replicated and better understood, for example, it could open the door to preventing addictions before they become harmful and cause irreparable harm, both physical and behavioral. Such an intervention would be unprecedented in the addiction field and would require additional research to identify greater risk factors for addictive behaviors, whether genetic, environmental, or behavioral, or a combination of these factors.

“The next big question is who benefits the most,” says Al-Aly. “At this point, we don’t really know. Are there subsets of people among this cohort of 600,000 people who might benefit more from GLP-1s? We would need additional follow-up studies.”