What to know about how GLP-1 medications might fight addiction

The blockbuster GLP-1 drugs that have reshaped the treatment of diabetes and obesity may help prevent multiple substance use disorders — and reduce the tragic outcomes they cause, a large new study finds.

An analysis published Wednesday in a medical journal looked at electronic health records from more than 600,000 U.S. Veterans Affairs patients with diabetes. It found that those treated with medications such as Ozempic and Mounjaro were less likely to develop addictions to alcohol, nicotine, cocaine, opioids and other substances than those treated with a different class of drugs.

In those already addicted, the GLP-1 drugs were linked to lower risks of hospitalization, overdose and death, according to the study.

The new results suggest — but don’t prove — that the weight-loss medications may be able to target the underlying source of cravings that affect the more than 48 million Americans with substance use disorders.

“They’re actually working against the root cause of all these different addictions,” said Dr. Ziyad Al-Aly, the study’s lead author and a chief researcher at the VA St. Louis Health Care System.

Here’s what you need to know about the new research published by The BMJ:

How the study was designed

Previous studies have suggested that the drugs known as GLP-1s, or glucagon-like peptide-1 receptor agonists, could reduce addictions by targeting the brain’s reward pathways. But those studies have been small and often limited to one substance.

For this study, one of the largest to date, Al-Aly and his colleagues analyzed data from the electronic records of more than 600,000 Veterans Affairs patients with diabetes over three years. They compared people who received GLP-1 drugs with those treated with medications that lower blood sugar.

The patients were divided into seven parallel trials that analyzed the risk of developing addictions to multiple substances including alcohol, cannabis, cocaine, nicotine and opioids. Another trial looked at the risk of specific harms among people with existing addictions when they took the different types of medication.

What the researchers found

Al-Aly and his colleagues found that people starting the GLP-1 drugs had lower risks of developing addiction to multiple substances. Compared with the other medications, people taking the GLP-1 drugs had a reduced risk for addiction: 18% for alcohol, 14% for cannabis, 20% for both cocaine and nicotine, and 25% for opioids.

In patients who already had substance use disorders, starting the GLP-1s was linked with a 31% lower risk of emergency department visits, 26% lower risk of hospitalizations, 25% lower risk of suicidal thoughts or attempts, 39% lower risk of overdose — and 50% lower risk of death.

Overall, the study found that using GLP-1 drugs likely prevented about seven cases of substance use disorder and 12 incidents involving serious harm for every 1,000 users over three years, Al-Aly said.

The limits of the study

Among the study’s limitations: It was conducted within the VA health system, which serves a population that is mostly older, white and male, although Al-Aly said the results were consistent in more than 35,000 women. It also includes data only from people with diabetes, not the general population.

The researchers also couldn’t account for some factors, such as socioeconomic status or lifestyle choices, that could affect the results. And the analysis focuses on the effects of using GLP-1s compared with another drug, not compared with no treatment.

As an observational study, the new analysis showed that the GLP-1s are associated with reduced risk of substance use disorders and harms, not that the drugs themselves caused the reduction.

Addiction researchers see a need for new medications

The new findings are striking, said Dr. Lorenzo Leggio, a National Institute on Drug Abuse clinical director who wasn’t involved in the study.

“Even though we don’t fully understand the mechanism, somehow the GLP-1 system is tackling addiction biology and the foundational system that underlies all these disorders,” he said.

Diabetes and weight-loss trials have shown that the GLP-1 drugs target hormones in the gut and the brain that control appetite and feelings of fullness, cutting down on what’s described as “food noise,” or intrusive thoughts of food. In the same way, this study indicates the drugs may tamp down “alcohol or drug noise,” Leggio said.

Growing evidence that GLP-1s might prevent substance use disorders is exciting, said Dr. Anna Lembke, a Stanford University addiction medicine specialist.

“We haven’t really had a new tool in our toolbox from a pharmacotherapy perspective to treat addiction in a long time,” said Lembke, noting that some addiction specialists are already prescribing GLP-1s off-label, especially when other treatments have failed.

She cautioned that the GLP-1 drugs don’t work the same way for all users and that they have risks that must be weighed against potential benefits.

What comes next

The new findings do not, by themselves, justify prescribing GLP-1 drugs to prevent or treat substance use disorders, Al-Aly said. That evidence would need to come from randomized controlled clinical trials that directly compare the use of the drugs against a placebo, or dummy medication. Several such trials are pending, Leggio noted.

The goal is finding a new way to treat addictions, which are a leading cause of sickness and death around the world.

“The consequence in terms of chronic disease of these addictive drugs is actually gigantic in our society,” Leggio said.

___

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation. The AP is solely responsible for all content.