Ozempic and Similar Drugs Can Reduce The Risk of Substance Dependence By Up to 75%

What if a weight-loss drug also helped fight chemical dependency? A large study found that users of Ozempic and similar medications showed a striking reduction in the risk of developing dependence on alcohol, nicotine, opioids, and other drugs. The results are leading scientists to investigate a new way to treat addiction by acting directly on the brain's reward circuits.

Drugs in the class of glucagon-like peptide-1 receptor agonists, which include popular drugs like semaglutide and liraglutide, have become known in recent years for their effectiveness in treating obesity and type 2 diabetes. However, researchers are discovering that their effects may go far beyond weight loss and glucose control.

A new study suggests that these medications may be associated with a striking reduction in the risk of developing different forms of chemical dependency.

Substance use disorders represent one of the greatest challenges to global public health. Alcohol, nicotine, opioid, cocaine, and other drug addiction affects millions of people and is associated with psychological distress, physical illness, family difficulties, loss of productivity, and increased mortality.

Although treatments are available, relapse rates remain high, and many people continue to face difficulties maintaining long-term recovery.

Scientists' interest in glucagon-like peptide (GLP) drugs arose when animal studies began to show something unexpected. In addition to controlling appetite, these drugs also appear to influence brain regions linked to reward and motivation.

These areas include structures such as the ventral tegmental area and the nucleus accumbens, central components of the so-called brain reward system, responsible for the sensation of pleasure and the reinforcement of behaviors.

Under normal conditions, this system helps motivate activities important for survival, such as eating and social interaction. However, drugs of abuse can hijack this circuit, causing intense releases of dopamine, a neurotransmitter associated with reward. Over time, the brain begins to compulsively seek the substance, favoring the development of dependence.

Experimental studies suggest that GLP agonists may reduce this dopaminergic hyperactivation, decreasing craving and compulsive drug-seeking behavior.

To investigate whether this effect could also be observed in humans, researchers analyzed data from the All of Us research program, one of the largest health databases in the United States. Instead of conducting a traditional clinical trial, the scientists used a method called a nested case-control retrospective study.

In simple terms, they analyzed existing medical records and compared people with type 2 diabetes or obesity who developed substance use disorders with similar individuals who did not develop these disorders.

The study involved tens of thousands of participants. Researchers identified individuals who had received diagnoses of alcohol, opioid, nicotine, or cocaine use disorders and compared their medical histories with those of people without these diagnoses.

Then, they checked how many participants were using medications from the class of glucagon-like peptide receptor agonists before the onset of substance use disorders.

The results were noteworthy. The use of these medications was associated with an approximately 74% reduction in the likelihood of developing alcohol use disorder. For opioid dependence, the observed reduction was about 69%. For nicotine use disorders, the decrease was approximately 68%. In the case of cocaine, the reduction reached 75%.

When researchers analyzed the overall risk of any substance use disorder, users of these medications were about 75% less likely to develop dependence compared to those who did not use the medication.

Despite the promising results, the authors emphasize that the study does not prove a cause-and-effect relationship. As it is an observational analysis, it is not possible to state with certainty that the medications were directly responsible for the risk reduction. Other factors may have influenced the results.

Nevertheless, the findings strengthen a growing line of research suggesting that these medications may act not only on metabolism, but also on brain circuits involved in impulse control, reward, and compulsive behaviors.

If future clinical trials confirm these results, medications originally developed to treat obesity and diabetes could become important tools in combating chemical dependency. This would open a new therapeutic approach to a problem that continues to affect millions of people worldwide.

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Association between GLP-1 receptor agonist use and substance use disorders among individuals with type 2 diabetes or obesity: a nested case-control study in the All of Us research program

Tadesse M. Melaku Abegaz, Muktar Ahmed, Akshaya Srikanth S Bhagavathula, and Gabriel Frietze, 

Frontiers in Psychiatry. Volume 17 - 2026 DOI: 10.3389/fpsyt.2026.1766770

Abstract: 

Objectives: The current study evaluated the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and substance use disorders (SUD) in type 2 diabetes and obesity.Methods: We conducted a retrospective nested case-control study using the All of Us Research Program data. Cases were defined as diabetes/obese individuals with a new diagnosis of alcohol use disorder (AUD), opioid use disorder (OUD), nicotine use disorder (NUD), or cocaine use disorder (CUD). Control participants were drawn from individuals with diabetes or obesity who had no documented history of SUD. Conditional logistic regression was performed to estimate the association between SUD and GLP-1 RA exposure.Results: The study included a total of 22,652 participants in the AUD group, 13,226 in the OUD group, 42,320 in the NUD group, and 9,296 in the CUD group; each group comprised both cases and matched control participants. GLP-1 RA use was associated with a 74% reduction in the odds of AUD (odds ratio [OR] = 0.26; 95% confidence interval [CI]: 0.20–0.34), a 69% reduction in the odds of OUD (OR = 0.31; 95% CI: 0.23–0.42), a 68% reduction in the odds of NUD (OR = 0.32; 95% CI: 0.27–0.39), a 75% reduction in the odds of CUD (OR = 0.25; 95% CI: 0.16–0.40), and 75% lower odds of any SUD compared with non-users participants (OR = 0.25, 95% CI 0.22–0.30).Conclusions: GLP-1 RA use was consistently associated with lower odds of developing SUDs among individuals with type 2 diabetes or obesity. These findings suggest potential for GLP-1 RAs to help mitigate SUD in these populations.