Four existing medicines have been identified as the leading candidates for repurposing as Alzheimer’s disease treatments, with two already selected to enter the first arms of a new adaptive trial.
The drugs, atomoxetine, metformin, isosorbide mononitrate and levetiracetam, were chosen through a systematic pipeline developed for the Alzheimer’s Disease Systematic Multi-Arm Adaptive Randomised Trial (AD-SMART). Atomoxetine and metformin were selected for the initial active trial arms.
The findings were published in Alzheimer’s & Dementia [link here] by a team from Imperial College London led by Sabahat Iqbal, Cristina Bonet Olivares and Laura Rizzo.
Drug repurposing within adaptive platform trials offered “a promising approach” to make drug discovery more efficient and inclusive, the authors said, citing a 2025 review showing that one in three drugs tested in Alzheimer’s clinical trials were repurposed, and that nearly three-quarters of repurposing trials were publicly funded.
AD-SMART uses a multi-arm, multi-stage randomised adaptive design, allowing multiple drug candidates to be tested simultaneously against a shared placebo group. Therapies can be added or removed over time, reducing recruitment demands and costs compared with conventional single-drug trials. Similar designs have already been used in motor neurone disease, Parkinson’s disease and cancer.
To identify candidates, the team invited researchers from across the Alzheimer’s community to propose compounds using a standardised template. Fourteen proposals were presented to an international expert panel comprising clinicians, scientists, industry professionals, a charity representative and a patient and public representative.
Panellists independently ranked the compounds twice, based on biological plausibility, preclinical efficacy, safety and trial feasibility.
The authors acknowledged limitations. Standardised templates and predefined criteria helped reduce bias, but panel members discussed compounds and made decisions based on presentations by drug proposers or fellow panellists. The lack of anonymity and use of real-time video calls could have “increased social pressure and selection bias,” they said.
The process created a “scalable and adaptable pipeline” that provided “a strong foundation for future drug repurposing trials,” the authors concluded.