New study finds Ozempic patients have a 42%-68% lower risk of opioid overdose

Patients with OUD taking Ozempic have dramatically lower risk of opioid overdose compared to those taking other diabetes medications

A new study published this morning in JAMA Network Open shows large reductions in the likelihood of opioid overdose among patients receiving semaglutide (Ozempic) for diabetes compared to other diabetes medications. This is the fourth paper this year from Dr. Rong Xu and co-authored by NIDA Director Nora Volkow showing dramatically lower risks of substance use disorders among patients receiving semaglutide. 

Dr. Rong Xu, associate professor in the Department of Population and Quantitative Health Sciences at Case Western

“In this study, we observed a 40%-60% reduction in opioid overdose for semaglutide compared with other anti-diabetics, including other GLP-1RAs in patients with OUD and comorbid type 2 diabetes. These findings provide real-world evidence supporting future randomized clinical trials and mechanistic studies,” Dr. Xu told us.

This study adds to the rapidly accumulating body of evidence from randomized controlled trials and patient health record studies showing broad reductions in craving and consumption of alcohol, opioids, nicotine, and cannabis among people taking current generation GLP-1 medications like semaglutide.

The paper looks at patient health records for 33,006 patients who had a diagnosed opioid use disorder (OUD) as well as type 2 diabetes (T2D). It found that patients receiving Ozempic vs. other diabetes medications had between a 32% to 68% lower risk of opioid overdose, compared to other treatments.

Specifically, OUD patients receiving Ozempic have a 54% lower risk of opioid overdose than those taking metformin, a 58% lower risk than insulin alone, a 63% lower risk compared to DPP-4i, and a 42% lower risk compared to SGLT2i.

Crucially, this finding is both a positive and unintended effect of Ozempic in this patient population, suggesting that Ozempic reduces use of opioids even among patients who are not taking it for that purpose.

From the paper:

Semaglutide was associated with a significantly lower risk of opioid overdose during a 1-year follow-up compared with other antidiabetic medications, including other GLP-1RAs, with HRs ranging from 0.32 (95% CI, 0.12-0.89) to 0.58 (95% CI, 0.38-0.87). The negative control outcome showed no difference between groups.

Additional research may be able to examine opioid overdose rates among patients who do not have a diagnosed OUD, as there may be preventative effects similar to those seen in alcohol use disorder.

Here’s the key figure:

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New results are consistent with previous findings for alcohol, cannabis, and nicotine

In a statement, Dr. Volkow said, “The preliminary findings from this study point to the possibility that GLP-1 medications may have value in helping to prevent opioid overdoses.”

These results are consistent with previous GLP-1 patient record studies from the formidable duo of Rong Xu and Nora Volkow. Their recent papers are:

• Alcohol: 50-56% decrease in the risk of new or recurring alcohol addictions among people taking semaglutide

• Cannabis: 30-50% decreases in new and recurrent CUD in patients with diabetes or obesity who were treated with semaglutide vs non-GLP-1 medications

• Smoking: Patients who began taking semaglutide were then 68% less likely to later receive a prescription for a smoking cessation medication

• Suicidal ideation: 66 - 73% lower risk of suicidal ideation for patients receiving GLP-1RAs

Upcoming papers from Dr. Xu will look at semaglutide for stimulant use disorder, depression, and other mental health conditions.

Today’s paper has been added to our comprehensive review of the medical evidence for GLP-1s and addiction, which is the most up to date resource anywhere.

What about Mounjaro, Zepbound, and Wegovy?

Note that this study did not include the newest GLP-1RA for diabetes, Mounjaro (tirzepatide), which has not been available long enough for sufficient patient data to be available for this study. Most scientists in the field believe that tirzepatide likely has comparable anti-addictive properties to semaglutide, potentially with lower side effects.  There is at least one study planned to compare semaglutide and tirzepatide directly in SUD patients.

This study also did not look at semaglutide or tirzepatide for obesity (Wegovy and Zepbound) because there are no other obesity medications widely used by patients to serve as comparison. There are some indications that OUD may be associated with obesity, where use of GLP-1’s is at least double the overall population rate. Roughly 6% of American adults currently taking a GLP-1 for any reason and that number is rising quickly. These trends may lead to measurable population-level reductions in opioid consumption and overdose rates over time. Morgan Stanley has already forecast a decline in future alcohol consumption based on the trend of GLP-1 adoption.

The research we need next 

Despite the accumulating evidence, Novo Nordisk and Eli Lilly (owners of Ozempic and Mounjaro, respectively) have no plans to conduct large-scale phase 3 trials of these medications for substance use disorders. This means that most substance use disorder patients are left with no way to access these drugs, because insurance will not pay for coverage without official FDA approval. The patients in this study had access only because they also had type 2 diabetes, which is a use that insurance will cover.

Addiction to cigarettes, alcohol, opioid, and stimulants kills 767,000 Americans every year (more than cancer or heart disease). And yet, what may the biggest breakthrough in addiction medicine in the past 50 years is stuck in limbo, without a path to broad access for patients.

We believe the public must step up.

This is why our organization, CASPR, has formed a coalition to advance phase 3 trials of GLP-1s for addiction. We are in the process of raising funding and building the scientific and operational team to conduct these trials. If you can help, please be in touch.

Coming tomorrow! A new interview with an addiction medicine doctor who has made GLP-1s a core part of his practice. You can subscribe to Recursive Adaptation below (it’s 100% free) to get an email when the article is published.