Semaglutide for Treatment of People With Methamphetamine Use Disorder: the SHIFT Study (SHIFT)

Methamphetamine use disorder is a major public health concern in Australia and globally. GLP-1 medications such as semaglutide (e.g. Ozempic) are approved for diabetes and medication, and may potentially affect craving for other substances apart from food. We do not know if this will help people who use methamphetamine ('ice') to reduce their use. This study will treat people who use methamphetamine with weekly injections of semaglutide. It will provide data on if this is a potentially safe and practical treatment for this group of people.

Study Overview

• Status: Not yet recruiting
• Conditions: Methamphetamine Use Disorder
• Intervention / Treatment: Drug: 12 weeks of weekly subcutaneous semaglutide injection

Detailed Description

Methamphetamine use disorder is a major public health concern in Australia and globally, associated with high morbidity and limited treatment options. People with methamphetamine use disorder frequently face social marginalisation, psychiatric comorbidity, housing instability, and criminal justice involvement, contributing to poor treatment access and outcomes. At present, no pharmacotherapies have been approved for the treatment of methamphetamine use disorder. While several agents have demonstrated preliminary promise-including mirtazapine, which has shown consistent findings across trials-none have yet established sufficient efficacy to achieve regulatory approval. Ongoing registrational trials, such as those evaluating extended-release naltrexone combined with bupropion, and mirtazapine, may clarify the potential role of these agents in clinical practice.

Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide, are approved for diabetes and obesity and have central effects on reward pathways relevant to addiction. Preclinical studies show GLP-1 agonists reduce stimulant-related dopamine signalling and drug-seeking behaviour. Observational studies in humans suggest semaglutide may reduce risk of alcohol use disorder, hospitalisations related to substance use, and overdose, and a recent randomised controlled trial demonstrated reductions in cravings, and use of, alcohol and tobacco. However, no trials have yet evaluated semaglutide in methamphetamine use disorder. This pilot study will be the first to assess its feasibility, safety, and preliminary efficacy for methamphetamine use disorder.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Goodman-Meza, MD, PhD; Phone Number: +61-403-995-056; Email: dgoodman@kirby.unsw.edu.au

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Kirketon Road Centre
      • Principal Investigator: Phillip Read
      • Contact: Phillip Read; Phone Number: +61 2 9360 2766; Email: Phillip.Read1@health.nsw.gov.au
    • Darlinghurst, New South Wales, Australia, 2010
      • Rankin Court Treatment Centre, St Vincent's Hospital Sydney
      • Contact: David Goodman-Meza, MD, PhD; Email: dgoodman@kirby.unsw.edu.au
      • Principal Investigator: David Goodman-Meza
  • Queensland
    • Brisbane, Queensland, Australia, 4000
      • Alcohol & Drug Service, Metro Health North Brisbane
      • Contact: Mark Daglish; Phone Number: +617 3837 5764; Email: mark.daglish@health.qld.gov.au
      • Principal Investigator: Mark Daglish
  • South Australia
    • Morphett Vale, South Australia, Australia, 5162
      • Drug and Alcohol Services, South Australia
      • Contact: Katherine Senior; Phone Number: +618 8325 8111; Email: Katherine.Senior@sa.gov.au
      • Principal Investigator: Katherine Senior
  • Western Australia
    • East Perth, Western Australia, Australia, 6004
      • Next Step Drug and Alcohol Services
      • Contact: Michael Christmass; Phone Number: +6189430 5966; Email: michael.christmass@health.wa.gov.au
      • Principal Investigator: Michael Christmass

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has provided voluntary, written informed consent;
2. Aged 18 years or older;
3. Diagnosed with moderate to severe methamphetamine use disorder (DSM-5 criteria);
4. Self-reported methamphetamine use on at least 14 of past 28 days and a positive oral fluid drug screen for amphetamine/methamphetamine;
5. Willing and able to comply with study procedures and follow-up visits;
6. People of child-bearing potential must agree to use effective contraception during treatment and during the 60 days after treatment end.

Exclusion Criteria:

1. Uncontrolled medical or psychiatric conditions that may interfere with participation;
2. Body mass index less than 22 kg/m2;
3. Confirmed diagnosis of diabetes mellitus (either known history of diabetes; concomitant treatment with insulin, metformin, sulfonylureas, thiazolidinediones, SGLT2 inhibitor, DPP4 inhibitor; or HbA1c >6.5 at screening);
4. Currently taking a GLP-1 receptor agonist;
5. Known hypersensitivity or contraindications to GLP-1 receptor agonists as per product information;
6. Current enrolment in another interventional trial;
7. Lactating, pregnant or at risk of pregnancy not willing to avoid pregnancy
8. History of pancreatitis;
9. History of medullary thyroid cancer;
10. Current admission to a residential rehabilitation program or inpatient program or planned admission during the study period, which would interfere with participation in study visits or procedures;
11. Currently experiencing psychosis or current active suicidality
12. Any condition or circumstance that, in the opinion of the investigator, would compromise the participant's ability to comply with the study procedures, complete protocol requirements, or provide reliable data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adults with methamphetamine use disorder; 12 weeks of subcutaneous semaglutide administered once weekly	Drug: 12 weeks of weekly subcutaneous semaglutide injection; 12 weeks of subcutaneous semaglutide administered once weekly, starting at 0.25 mg once weekly, titrated as tolerated up to 1.0 mg over the 12-week study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Outcome (exploratory)	Last 4-week methamphetamine use measured by the TLFB method at week 12 compared to screening	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary exploratory outcome	Total number of days of self-reported methamphetamine use	12 weeks
Secondary exploratory outcome	End-of-treatment abstinence from methamphetamine (self-reported and oral fluid drug screens);	12 weeks
Secondary exploratory outcome	Use of, and end-of-treatment abstinence from, other substances (e.g., opioids, benzodiazepines, tobacco, alcohol).	12 weeks
Secondary exploratory outcome	Change in methamphetamine craving score on visual analogue scale	12 weeks
Secondary exploratory outcome	Weight loss	12 weeks
Secondary exploratory outcome	Retention in opioid agonist treatment (OAT) programs at 12 weeks (for those enrolled in OAT)	12 weeks
Secondary exploratory outcome	Change in health-related quality of life utility score on the EQ-5D-5L	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - recruitment	Recruitment: Number of participants screened, proportion enrolled, reasons for exclusion.	Screening to week 14 end of study follow up visit
Feasibility - retention	Retention: Proportion completing the 12-week study; time-to-dropout; comparison of baseline characteristics of completers vs. non-completers.	Screening to week 14 end of study follow up visit
Feasibility - adherence	Adherence to the intervention: Number and proportion of scheduled semaglutide doses received (in-clinic and self-administered).	Baseline to week 12
Feasibility - data completeness	Data completeness: Proportion of participants with complete data at each timepoint for Timeline Follow Back (primary exploratory efficacy outcome), and quality of life	Screening to week 14 end of study follow up visit
Feasibility - acceptance	Tolerability and perceived benefit: Proportion of participants who remain on semaglutide through week 12; rates of treatment discontinuation due to adverse events; and participant-reported perceptions of tolerability and benefit, captured using the Treatment Effectiveness Assessment (TEA) at week 12.	Baseline to week 12
Safety - adverse events	Incidence, severity, and type of treatment-related adverse events and serious adverse events during the treatment period.	12 weeks
Safety - treatment-related serious adverse events	Proportion of participants experiencing at least one treatment-related serious adverse event or discontinuing treatment due to an adverse event related to the study medication.	12 weeks

Collaborators and Investigators

• Sponsor: Kirby Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: March 28, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; Semaglutide; Addiction; Drug use; Stimulants; Methamphetamine; Substance use disorder; Ozempic; Wegovy
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Compulsive Behavior; Impulsive Behavior; Behavior; Substance-Related Disorders; Behavior, Addictive
• Other Study ID Numbers: VHCRP2502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No