Incretin-based therapies in psychiatry: A landscape analysis of ongoing randomized trials registered on ClinicalTrials.gov

Incretin-based therapies, including conventional glucagon-like peptide-1 receptor agonists (GLP-1RAs) and GLP-1-containing co-agonists, are being repurposed for psychiatric disorders. The breadth and maturity of the randomized pipeline are easily misread.

We searched ClinicalTrials.gov on 1 September 2026 for ongoing randomized trials in which a psychiatric disorder or addictive behaviour was central to recruitment and a psychiatric or behavioural outcome was registered as primary or co-primary. The search queried the intervention field for 56 named agents and development codes and all record fields for five mechanism phrases, with an automated audit for agents absent from the term list. Trials with metabolic endpoints in psychiatric populations, neurocognitive trials, and non-randomized studies were catalogued separately.

Thirty-four ongoing randomized trials met the core criteria, with a planned enrolment of 8519 participants; 25 (74%) were recruiting, 21 were phase 2 and six phase 3. Three compounds accounted for the entire pipeline, and 17 trials (50%) tested a GLP-1-containing co-agonist. Targets were alcohol use disorder (14 trials; n = 3686), major depressive disorder (3; n = 2116), opioid use disorder (4; n = 1021), tobacco or nicotine use (5; n = 708), bipolar disorder (1; n = 400), cannabis (3; n = 206), methamphetamine (1; n = 162), cocaine (2; n = 115), and binge-eating disorder (1; n = 105). Twenty-nine trials concerned addiction or tobacco use, and seven trials of a single co-agonist from one sponsor accounted for 62% of planned enrolment. Six further trials in schizophrenia-spectrum disorders registered metabolic rather than psychiatric primary endpoints.

The ClinicalTrials.gov-registered psychiatric pipeline is larger than previously described but remains concentrated in addiction, and almost all development outside addiction belongs to one manufacturer's programme, which is proceeding without a positive randomized result in any psychiatric indication. Half of all trials use co-agonists, so a positive result would not identify the responsible mechanism.