Semaglutide for Opioid Use Disorder

(SHORE Trial)

Overseen By Joji Suzuki

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Buprenorphine

Must not be taking: GLP-1 agonists

Disqualifiers: Substance use disorder, Diabetes, Eating disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 12 weeks

46 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue taking buprenorphine during the study. You cannot use any GLP-1 agonist medications during the trial.

What evidence supports the effectiveness of the drug Semaglutide for treating opioid use disorder?

Research on similar drugs, like liraglutide, shows that they can reduce drug-seeking behavior in rats for opioids like heroin and fentanyl. These drugs work by targeting GLP-1 receptors, which are involved in regulating hunger and can also influence drug-seeking behavior. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used for type 2 diabetes under names like Ozempic and Rybelsus, has been shown to be generally safe in humans, with common side effects including gastrointestinal issues. It has been tested in large clinical trials and is considered safe for the heart in high-risk patients. ^{6 7 8 9 10}

How is the drug Semaglutide unique in treating opioid use disorder?

Semaglutide, a glucagon-like peptide-1 receptor agonist, is unique for opioid use disorder as it offers a non-opioid alternative that may reduce drug-seeking behavior by targeting brain receptors involved in satiety, unlike traditional treatments that often involve opioids themselves. ^{2 3 4 11 12}

What is the purpose of this trial?

The is a pilot, 12-week, double-blind, placebo-controlled, randomized trial of individuals with opioid use disorder (OUD) newly initiating buprenorphine to receive either weekly injections of semaglutide (n=23) or matching placebo (n=23). The primary aim is to determine the effects of semaglutide on cue-reactivity among individuals with OUD. The secondary aim is to assess the preliminary efficacy, safety, and tolerability of semaglutide for OUD.

Eligibility Criteria

This trial is for individuals starting treatment with buprenorphine for opioid use disorder. Participants will be randomly assigned to receive either semaglutide or a placebo in weekly injections over 12 weeks.

Inclusion Criteria

DSM-5 diagnosis of opioid use disorder, severe

I started taking buprenorphine under the tongue within the last 60 days.

Anticipating continuation of SL-BUP for the duration of the trial

Exclusion Criteria

Psychotic disorder, active suicidality or homicidality or any psychiatric condition that impairs ability to provide informed consent

BMI < 25mg/kg2

I have been diagnosed with diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline procedures including neurocognitive testing and initial assessments

1 week

1 visit (in-person, 3 hours)

Treatment

Participants receive weekly injections of semaglutide or placebo, with dose adjustments

12 weeks

13 visits (in-person, weekly)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person, 3 hours)

Treatment Details

Interventions

• Semaglutide

Trial Overview The study tests if semaglutide affects cravings and reactions to drug cues in people with opioid addiction. It's also looking at how safe and tolerable the drug is as a potential treatment option.

Participant Groups

Group I: Semaglutide Experimental Treatment 1 Intervention

This arm will receive semaglutide (n=23). All participants will initially receive 0.25mg for 4 weeks, and then as tolerated dose will be increased to 0.5mg for 4 weeks. Then as tolerated, the dose will be increased to 1.0mg for 4 weeks.

Group II: Placebo Placebo Group 1 Intervention

This arm will receive saline placebo (n=23).

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

The study found that the GLP-1 analog liraglutide, when administered acutely, effectively reduced heroin-seeking behavior in rats exposed to drug cues, stress, and the drug itself, suggesting its potential as a nonopioid treatment option.

Liraglutide did not impair locomotor function, indicating that its effectiveness in reducing drug-seeking behavior is not due to decreased physical performance, which supports its safety as a treatment bridge for opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats. Douton, JE., Acharya, NK., Stoltzfus, B., et al.[2023]

GLP-1 receptor (GLP-1R) agonists show promise as a new treatment for opioid use disorder (OUD), potentially helping to prevent relapse, which is a major challenge in current OUD therapies.

A novel dual agonist that targets both GLP-1Rs and neuropeptide Y2 receptors (Y2Rs) has been found to reduce fentanyl use in rats without the adverse effects seen with GLP-1R agonists alone, suggesting a more effective treatment strategy for OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y2 receptors. Merkel, R., Moreno, A., Zhang, Y., et al.[2022]

Acute treatment with the GLP-1 receptor agonist, liraglutide, significantly reduced both cue-induced and drug-induced seeking behavior for fentanyl in rats, suggesting its potential as a non-opioid treatment for Opioid Use Disorder (OUD).

The efficacy of liraglutide in reducing fentanyl seeking was comparable to that of buprenorphine, a currently approved partial opioid agonist, indicating that GLP-1 may be a promising new target for OUD therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, reduces cue- and drug-induced fentanyl seeking in rats. Urbanik, LA., Acharya, NK., Grigson, PS.[2022]

In a rodent model, the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide effectively reduced both cue-induced and drug-induced heroin seeking behaviors, suggesting its potential as a treatment to prevent relapse in opioid use disorder.

The titration regimen of liraglutide did not affect glucose or insulin levels, indicating that it may provide a non-opioid option for relapse prevention without the common side effects associated with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose titration with the glucagon-like peptide-1 agonist, liraglutide, reduces cue- and drug-induced heroin seeking in high drug-taking rats. Evans, B., Stoltzfus, B., Acharya, N., et al.[2023]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

Over 2 million Americans have opioid use disorder, which is partly due to overprescribing, highlighting the need for better opioid stewardship and management strategies by physicians.

Three FDA-approved medications—methadone, buprenorphine, and naltrexone—are effective for treating opioid use disorder, but successful outcomes are best achieved through comprehensive, interprofessional management plans rather than relying solely on medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Drug and Alcohol Use Disorders: Opioid Use Disorder. Witt, L., Butler, F.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y2 receptors. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, reduces cue- and drug-induced fentanyl seeking in rats. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Dose titration with the glucagon-like peptide-1 agonist, liraglutide, reduces cue- and drug-induced heroin seeking in high drug-taking rats. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Activation of GLP-1 receptors attenuates oxycodone taking and seeking without compromising the antinociceptive effects of oxycodone in rats. [2021]

6. Belgium pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. [2019]

7. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Prescription Drug and Alcohol Use Disorders: Opioid Use Disorder. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

OREX-1019: A Novel Treatment of Opioid Use Disorder and Relapse Prevention. [2021]