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Do GLP-1 Drugs Help Opioid Use Disorder? No Trial Has Reported

The first randomized trial is enrolling 310 adults and has published only its design. The nearest completed trial, in alcohol, missed its prespecified primary outcome.

Wesley Jenkins8 min read
What has been published, and what has notdesignpublishedsample: 310, randomized 1:1publishedprimary outcome: 6-month retentionpublishedresultsnot yetNothing on this site is sold for opioid use disorder.

Nobody knows yet, and the honest answer is that short. The first randomized trial of a GLP-1 drug in opioid use disorder has published its design and nothing else [1]. What exists around it is one completed trial in alcohol whose main endpoint missed, and one observational cohort. Neither licenses a claim. The pattern is the one set out in what an addiction trial of these drugs can conclude.

What is being tested

The trial is enrolling 310 adults with moderate to severe opioid use disorder. All of them have recently started buprenorphine. They are randomized one to one to tirzepatide or placebo, with weekly research visits for six months. Longer assessments fall at one, three and six months, and a safety visit at week 30.

Randomization is balanced by site and by buprenorphine formulation. Buprenorphine is the treatment here. Tirzepatide is the adjunct under test, and the authors call this the first randomized trial of it in this condition.

The nearest completed trial missed its endpoint

Fifty adults with moderate to severe alcohol use disorder took oral semaglutide or placebo for eight weeks [2]. The dose ran 3 mg daily for four weeks, then 7 mg daily for four. The prespecified primary outcome was lab cue-elicited craving at week 6, and it did not move. Drinks per day did not move either.

Several secondary outcomes did. Heavy drinking days fell, b −0.580, 95% CI −1.012 to −0.148. Drinks per drinking day fell, −1.177, interval −2.307 to −0.047. Craving reported in daily life fell, −2.195, interval −4.174 to −0.216. Three of those upper bounds stop just short of no effect, and with 50 people a handful of different participants would erase them.

A trial with many outcomes usually produces a significant one. That is arithmetic rather than evidence, and the primary endpoint exists to stop the arithmetic from talking. The authors conclude that continued development is warranted, which is not a conclusion that it works. The full reading sits in the alcohol trial that missed.

What the observational evidence adds

A Swedish national cohort followed 95,490 people with depression or anxiety who were taking an antidiabetic drug, of whom 22,480 used a GLP-1 [3]. Semaglutide was associated with less worsening substance use disorder, adjusted hazard ratio 0.53, 95% CI 0.35 to 0.80.

Three limits apply to that number. It is a secondary outcome in an observational study. It describes semaglutide, and the drug being tested in opioid use disorder is tirzepatide, which that cohort did not include. And the design compares periods of use against periods of non-use in the same person, which removes fixed confounders and not time-varying ones. The molecule-by-molecule split is set out in four drugs in one class.

What a reader should do with this

Nothing on this roster is sold for opioid use disorder. Nobody should obtain tirzepatide to treat it. Participants in the trial receive it alongside proper treatment under supervision, which is not a situation a telehealth purchase reproduces.

The rule worth carrying is narrower than the subject. A drug with a real effect on one addiction endpoint may do nothing for a neighboring one. Only a trial that named its endpoint in advance can tell the two apart. Every new indication eventually becomes a marketing claim somewhere, which is why the gates a seller has to clear matter more than the claim does.

Frequently asked

Do GLP-1 drugs help opioid use disorder?
No trial has reported. The first randomized trial is enrolling 310 adults with tirzepatide added to buprenorphine, and only its design has been published.
What will that trial measure?
Its primary outcome is remaining on buprenorphine at six months. The proportion of opioid-negative urine samples is a secondary outcome, so the headline result will be about staying in treatment rather than about using less.
Did the alcohol trial work?
Its prespecified primary outcome, lab cue-elicited craving at week 6, was not significant, and neither was drinks per day. Heavy drinking days fell as a secondary outcome, b −0.580, 95% CI −1.012 to −0.148, in 50 people over eight weeks.
Is there any evidence outside trials?
A Swedish cohort of 95,490 people linked semaglutide to less worsening substance use disorder, adjusted hazard ratio 0.53, 95% CI 0.35 to 0.80. It is observational, semaglutide only, and did not include tirzepatide.
Can I buy a GLP-1 for this?
Nothing on this roster is sold for opioid use disorder, and nobody should obtain one to treat it. Trial participants receive it alongside buprenorphine under supervision.

Sources

  1. [1] Winhusen TJ, et al. (2026). Evaluation of Tirzepatide as an Adjunct to Buprenorphine for the treatment of opioid use disorder (TAB) trial: study design and rationale Contemporary Clinical Trials. PMID 42600923
  2. [2] Schacht JP, et al. (2026). Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial The American Journal of Psychiatry. PMID 42522065
  3. [3] Taipale H, et al. (2026). Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study The Lancet Psychiatry. PMID 41862258

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