GLP-1 drugs protect against new or worsening addictions, large study shows

March 4 (Reuters) – Ozempic, Mounjaro and other GLP-1 drugs for diabetes can prevent the formation of new substance use disorders and alleviate existing addictions, according to findings from a large study of U.S. military veterans.

The protective effect was seen across a wide variety of addictive and habit-forming substances, including cocaine, opioids, alcohol, nicotine and cannabis, adding further evidence to a phenomenon previously flagged in smaller studies.

“That breadth was quite a surprise,” said Dr. Ziyad Al-Aly of the VA Saint Louis Health Care System in Missouri, who led the study published in The BMJ. “In addiction medicine, there’s not a single drug that works across all these substances.”

His team used a U.S. Veterans Affairs database to identify patients with type 2 diabetes treated with drugs from two different classes of medicines: GLP-1s such as Eli Lilly’s Trulicity or Mounjaro, and Novo Nordisk’s Victoza or Ozempic; and SGLT-2 inhibitors such as Jardiance from Boehringer Ingelheim and Farxiga from AstraZeneca. They then compared them in simulated randomized trials.

For the most part, study participants were not taking the higher-dose GLP-1 drugs used to treat obesity.

The 124,001 participants without a history of substance abuse who were taking GLP-1 drugs had 14% lower odds of developing a new substance use disorder over the following three years than the 400,816 similar patients prescribed SGLT-2 inhibitors.

GLP-1 drugs reduced the odds of new alcohol use disorders by 18%, cannabis use disorders by 14%, cocaine use by 20%, nicotine use by 26%, and opioid use by 25%, the researchers found. 

Among 81,617 patients with existing substance use disorders, the odds of related emergency department visits during the next three years were 31% lower for those on GLP-1s. GLP-1 drugs also reduced related hospital admissions by 26% versus the SGLT-2s, related deaths by 50%, drug overdoses by 39%, and suicidal ideation or attempt by 25%.

COMMON BIOLOGIC PATHWAY 

Doctors are taught that “if a patient has an addiction to substance A, you give them the antidote for substance A, such as a nicotine patch for tobacco, or naltrexone for alcohol,” Al-Aly said. 

“But here, you have this drug that is working across all addictive substances,” he continued. “That’s telling us that there is likely a common biologic pathway that is driving all of these addictions that is indeed druggable or treatable by GLP-1.”

The proteins on brain cells that receive chemical signals from GLP-1 drugs, known as GLP-1 receptors, are found in an area called the mesolimbic system that is responsible for motivation and reward signaling, Al-Aly noted.

The GLP-1 drugs are likely acting in the mesolimbic system to “put the lid on cravings” by silencing the noise in people’s brains that drive them toward overuse of foods or drugs, he said.

The researchers said they don’t know whether the effects will persist when people have been taking the drugs for many years, or whether the brain will adapt and the GLP-1 effects will weaken. 

“We’re very interested in fleshing this out and trying to understand this concept a little bit more,” Al-Aly said.

The VA itself is planning a large, traditional clinical trial testing semaglutide, the main ingredient in Ozempic and Wegovy, in U.S. veterans with alcohol use disorder.

“For patients with type 2 diabetes who also live with (or are at risk of) a substance use disorder, the key message is not to wait for a single ‘magic bullet,” Fares Qeadan of Loyola University in Chicago wrote in an editorial published with the study.

“These results suggest that when GLP-1 receptor agonists are clinically indicated for cardiometabolic reasons, potential benefits for substance related outcomes may be an added consideration in shared decision making.”

(Reporting by Nancy Lapid; Editing by Bill Berkrot)