# GLP-1 Drugs and Opioid Use Disorder: What the Records Data Shows

By Ruth Calder, Enforcement Editor (https://glpwatchdog.org/authors/ruth-calder) | Published: 2026-08-21 | Updated: 2026-10-27

Canonical page: https://glpwatchdog.org/research/glp1-and-opioid-use-disorder

> Across 503,747 people with opioid use disorder, a GLP-1 or GIP prescription carried an adjusted overdose rate ratio of 0.60. In methadone-treated patients it was associated with a higher rate of remission. No randomized trial exists.

## Key points

- 503,747 people with opioid use disorder: adjusted opioid-overdose rate ratio 0.60 (95% CI 0.43-0.83) with a GIP/GLP-1 prescription.
- In the same dataset, 817,309 with alcohol use disorder had an alcohol-intoxication rate ratio of 0.50.
- Among 1,157 methadone-treated patients, a GLP-1 was associated with entering remission (HR 1.75) and fewer myocardial infarctions (HR 0.58).
- Nobody has run a randomized trial of this; both studies rest on prescriptions and diagnosis codes.

No randomized trial has tested a GLP-1 for opioid use disorder. What exists is records data, and it points one way. Across 503,747 people with a history of opioid use disorder, those with a GLP-1 or GIP prescription had an adjusted opioid-overdose rate ratio of **0.60** (95% CI 0.43–0.83).[1] In a smaller, matched study of people already on methadone, a GLP-1 prescription was associated with a higher chance of entering remission (HR 1.75).[2] Both are associations. Neither is a reason to change an opioid treatment plan.

## The large cohort

The bigger study drew de-identified electronic health records from about 136 US health systems covering more than 100 million patients, from January 2014 to September 2022. It looked at 503,747 adults with a history of opioid use disorder and, separately, 817,309 with alcohol use disorder, comparing those with at least one GIP or GLP-1 receptor agonist prescription against those with none.[1]

*Adjusted incidence rate ratios with a GIP/GLP-1 prescription. Below 1 favors the prescription.[1]*

| Cohort | Outcome | aIRR | 95% CI |
| --- | --- | --- | --- |
| Opioid use disorder (503,747) | Opioid overdose | **0.60** | 0.43–0.83 |
| Alcohol use disorder (817,309) | Alcohol intoxication | **0.50** | 0.40–0.63 |

The association held when the analysis was restricted to people who also had type 2 diabetes and obesity. That matters because the obvious objection is that a GLP-1 prescription is a marker for having diabetes rather than a cause of anything. That subgroup consistency does not eliminate confounding, but it removes the simplest version of it.

> Every figure here comes from prescriptions and diagnosis codes. Somebody has to reach care and a clinician has to record an overdose for it to be counted, and a person receiving a weekly injectable is already engaged with a health system in a way many people with opioid use disorder are not. Adjusting or matching for demographics does not fix that difference.

## The methadone study

The second study is narrower and, for that reason, more interesting: everyone in it was already receiving methadone. It took adults on methadone with both opioid use disorder and type 2 diabetes from the TriNetX database between 2015 and 2024, propensity-matched them on baseline characteristics, and followed 1,157 people prescribed a GLP-1 for a year.[2]

*One-year hazard ratios in methadone-treated patients, after propensity matching.[2]*

| Outcome | HR | 95% CI |
| --- | --- | --- |
| **Entering opioid use disorder remission** | **1.75** | 1.24–2.47 |
| Myocardial infarction | 0.58 | 0.41–0.80 |
| Hypoglycemia | 0.50 | 0.33–0.77 |

In this design the GLP-1 sat alongside methadone, in people who were already receiving the treatment with the strongest evidence base there is. Nothing here suggests substituting one for the other, and nobody has studied that.

## What would settle it, and what to do meanwhile

- There is no randomized trial of a GLP-1 for opioid use disorder. Two observational studies pointing the same way is a reason to run one, not a reason to act as though it has been run.
- Buprenorphine and methadone are the treatments with randomized evidence for opioid use disorder. Nothing in this literature displaces them.
- The larger cohort found the same direction of effect for alcohol intoxication in a separate 817,309-person group, which is consistent with what has been seen for other substances.
- If you take an opioid agonist therapy, changes to it belong with the clinician managing it. A GLP-1 is not a substitute and was not studied as one.

For the same class of drugs across every other substance measured, including the randomized behavioral trial that missed its endpoints, see [GLP-1s and substance use](https://glpwatchdog.org/research/glp1-and-substance-use). For the one substance where a dedicated randomized cessation trial exists, see [GLP-1s and quitting smoking](https://glpwatchdog.org/research/glp1-and-quitting-smoking). The ten studies we would start with on the addiction question, alcohol included, are in [our substance use reading list](https://glpwatchdog.org/research/lists/top-glp1-addiction-substance-use-studies).

## Frequently asked questions

### Do GLP-1 drugs reduce opioid overdose risk?

In a records study of 503,747 people with opioid use disorder, those with a GIP or GLP-1 prescription had an adjusted opioid-overdose incidence rate ratio of 0.60, meaning about 40% lower recorded rates. That is an association from electronic health records, not a randomized result, and no trial has tested it.

### Is a GLP-1 a treatment for opioid use disorder?

No. It is not approved for that and there is no randomized evidence. Buprenorphine and methadone remain the treatments with trial support. In the study of methadone-treated patients, the GLP-1 sat alongside methadone rather than replacing it.

### What happened in people already on methadone?

Among 1,157 propensity-matched methadone-treated patients with opioid use disorder and type 2 diabetes, a GLP-1 prescription was associated with a higher rate of entering remission over one year (HR 1.75), along with fewer myocardial infarctions and less hypoglycemia.

### How reliable is this evidence?

Both studies are observational and rely on prescriptions and diagnosis codes. People prescribed a weekly injectable are already engaged with a health system in ways that adjusting or matching for demographics does not capture, which is the main reason these results need a trial before anyone acts on them.

## References

1. Qeadan F, McCunn A, Tingey B. The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. Addiction. 2025. PMID: 39415416. https://pubmed.ncbi.nlm.nih.gov/39415416/
2. Pan JY, Elman I, Panchal K, et al. GLP-1 Receptor Agonist Treatment and Health Outcomes in Methadone-Treated Patients with Opioid Use Disorder and Diabetes. Journal of General Internal Medicine. 2026. PMID: 42151525. https://pubmed.ncbi.nlm.nih.gov/42151525/

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Cite as: GLP Watchdog, Ruth Calder, "GLP-1 Drugs and Opioid Use Disorder: What the Records Data Shows", published 2026-08-21, updated 2026-10-27. https://glpwatchdog.org/research/glp1-and-opioid-use-disorder

Canonical HTML page: https://glpwatchdog.org/research/glp1-and-opioid-use-disorder

Medical disclaimer: Nothing here is medical advice. We report on this subject; we do not treat anyone. Whether to begin a medication, supplement, or treatment, whether to adjust it, and whether to stop are questions for a clinician licensed to answer them, who knows your history.