Semaglutide SHIFT Study to Evaluate Efficacy and Safety for Methamphetamine Use Disorder

Methamphetamine use disorder (MUD) represents a severe global public health crisis, characterized by compulsive use and high rates of relapse, with limited effective pharmacological treatments available. Current interventions primarily rely on behavioral therapies, which often have variable success rates and accessibility challenges. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, are well-established for managing type 2 diabetes and obesity due to their effects on glucose homeostasis and appetite regulation. Emerging preclinical and observational data suggest that GLP-1R activation may also modulate reward pathways in the brain, potentially reducing craving and drug-seeking behaviors for substances beyond food, including stimulants like methamphetamine. This mechanism offers a novel therapeutic avenue for MUD, addressing a critical unmet need for effective pharmacotherapy.

The SHIFT study is designed as a Phase 2, randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of semaglutide for treating methamphetamine use disorder. The study plans to enroll an estimated 162 participants who use methamphetamine. Participants will receive weekly subcutaneous injections of semaglutide or a placebo. The primary endpoint will focus on the reduction of methamphetamine use, likely measured through self-report and objective biological markers. This design aims to provide initial data on whether semaglutide is a safe and practical treatment option for this vulnerable population.