# Semaglutide for the treatment of opioid use disorder: A pilot randomized controlled trial

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $492,250

## Abstract

Abstract
The most effective treatment to tackle the ongoing opioid crisis in the US is buprenorphine, one of several
medications for opioid use disorder (OUD). Buprenorphine reduces overdose mortality by up to 70%, increases
treatment retention, and suppresses illicit opioid use, making it one of the most important interventions in
reversing the overdose epidemic. However, more than 30% will discontinue buprenorphine by 12 weeks due in
part to the emergence of craving for opioids, leading to relapse and heightened risk of an overdose.
Unfortunately, there are currently no evidence-based adjuncts to buprenorphine to reduce cue-reactivity and the
risk of early treatment discontinuation. Therefore, research to identify interventions that can be used as adjuncts
to buprenorphine is urgently needed. Glucagon-like peptide-1 (GLP-1) agonists, FDA-approved medications for
the treatment of diabetes and obesity, potentiate insulin release, inhibit glucagon release, delay gastric emptying,
and reduce food intake. The activation of GLP-1 receptors, which are highly expressed in the brain, reduce the
hedonic value of food and appear to have similar effects on reward valuation for substances of misuse, raising
the possibility that these medications could be repurposed for the treatment of OUD. Preliminary clinical studies
suggest GLP-1 agonists may impact substance use in humans, but these studies were based on older
formulations such as exenatide and liraglutide. The newer formulations such as semaglutide have greater
homology to native GLP-1 and are associated with fewer gastrointestinal adverse events. Data are therefore
lacking to validate the use of newer, more efficacious formulations in terms of safety profiles and initial impact
on cue-reactivity and OUD-related outcomes. Our central hypothesis is that semaglutide will demonstrate
attenuation of cue-reactivity providing preliminary evidence of its utility as an adjunct to buprenorphine to prevent
relapse. This proposal will be the first placebo-controlled randomized trial of the weekly formulation of
semaglutide as an adjunctive treatment to buprenorphine in individuals with OUD by evaluating cue-induced
craving. We will also study the safety and tolerability of semaglutide over the course of the 12-week trial. This
innovative R21 has public health impact because it will contribute to the identification of an effective
pharmacotherapy adjunct to buprenorphine for OUD and is highly responsive to the NIDA programmatic goals
of identifying novel treatment strategies for individuals with OUD. The NIDA Director has specifically cited the
need to conduct OUD research with medications with targets other than opioid receptors, and to repurpose
existing medications including GLP-1 agonists. If successful, results from this study will lay the groundwork for
the design of an adequately powered efficacy trial to determine whether semaglutide treatment can improve
OUD-related outcomes for those receiving buprenorph...

## Key facts

- **NIH application ID:** 11053820
- **Project number:** 1R21DA060304-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Joji Suzuki
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $492,250
- **Award type:** 1
- **Project period:** 2024-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11053820

## Citation

> US National Institutes of Health, RePORTER application 11053820, Semaglutide for the treatment of opioid use disorder: A pilot randomized controlled trial (1R21DA060304-01A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/11053820. Licensed CC0.

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