VA study links GLP-1 drugs to fewer overdoses and addiction deaths

A study of more than 600,000 veterans with type 2 diabetes found that those who started GLP-1 drugs had 50% fewer deaths tied to substance use and 39% fewer overdoses than veterans who did not start the medications, researchers reported in The BMJ ^[1]. The team followed patients in the U.S. Department of Veterans Affairs health system for three years ^[1].

GLP-1 drugs include semaglutide (sold as Ozempic, Wegovy and Rybelsus) and tirzepatide (Mounjaro and Zepbound) ^[1]. The study compared people who started one of these drugs with people who did not, adjusting for health history, demographics and other factors ^[1].

What the study found

Among veterans who already had a substance use disorder, those taking GLP-1 drugs had 50% fewer substance-related deaths, 39% fewer overdoses, 26% fewer drug-related hospitalizations and 25% fewer suicide attempts or thoughts of suicide ^[1]. The study also reported 31% fewer addiction-related emergency department visits ^[1]. Over three years, that worked out to about 12 fewer serious events per 1,000 people taking the drugs, including two fewer deaths ^[1].

Among veterans with no history of substance use disorder, the drugs were linked to a lower risk of developing one: 18% lower for alcohol use disorder, 25% lower for opioid use disorder, and about 20% lower for cocaine and nicotine dependence ^[1]. The study also found 14% lower risk for cannabis and 13% lower for other addictions ^[1]. That translated to roughly six to seven fewer new diagnoses per 1,000 GLP-1 users over three years ^[1].

The findings come from health records, not a randomized trial, so they show an association rather than proof that the drugs caused the changes ^[1]. The researchers said they applied the design of randomized trials to real-world data to lower the chance that other differences explained the results ^[1].

Why it matters for patients

Substance use disorders have few approved treatments, and none works across all substances, the researchers noted ^[1]. GLP-1 drugs are not approved for addiction, and there is not yet enough evidence to prescribe them for that purpose alone ^[1].

But many people already take these drugs for diabetes or obesity, conditions the drugs are approved to treat ^[1]. For a patient with diabetes who also wants to quit smoking, or a patient with obesity who also struggles with alcohol, the possible craving-related benefit is one more factor to weigh alongside the drug's approved uses ^[1]. The researchers described it as a potential extra benefit that other diabetes drugs do not offer, while stressing that it is not a proven addiction treatment ^[1].

The study points to a possible reason: GLP-1 drugs act on reward, motivation and stress circuits in the brain that addiction hijacks ^[1]. Animal studies show similar effects. Rodents given GLP-1 drugs drink less alcohol, take less cocaine and show less interest in nicotine, and monkeys given semaglutide drank less alcohol without signs of nausea ^[1].

The results line up with other research. A Swedish study of 227,000 people with alcohol use disorder found a 36% lower risk of alcohol-related hospitalization among those taking GLP-1 drugs -- more than double the 14% reduction linked to naltrexone, the best-performing approved medication in that analysis ^[1]. A randomized trial found semaglutide reduced both craving and alcohol consumption in people with alcohol use disorder, and another found dulaglutide reduced drinking ^[1].

What happens next

GLP-1 drugs have no approval for addiction, and more than a dozen trials testing them for substance use are underway or enrolling ^[1]. It is not known whether the benefits would continue over years of use, or what happens to cravings after someone stops taking the drug, as often happens with weight loss ^[1]. Researchers also have not settled whether long-term use might dull motivation in some people ^[1].