Researchers have begun recruiting 1,200 people for a pioneering dementia study that will test two existing medicines — the ADHD drug atomoxetine and the diabetes drug metformin — against Alzheimer's disease. The trial aims to halve the time required to test promising treatments by evaluating multiple drugs at once.
Patients will be randomly assigned to receive either a placebo, atomoxetine, or metformin. If successful, the treatments could be rolled out for dementia much sooner than new medicines that have not previously been tested in humans.
Multi-arm approach to speed up testing
Experts expect to add more drugs — both existing and new — to the study in the coming years. They likened the traditional approach of testing only one drug against a placebo to building a football stadium to play a single match.
Multi-arm trials have been successfully used for cancer, motor neurone disease, and to find Covid treatments during the pandemic.
Chief investigator Professor Paresh Malhotra, of Imperial College London, said a new approach was needed because “we just are not testing the most promising treatments for Alzheimer’s disease quickly enough, and we are not getting enough people with clinical Alzheimer’s disease into trials”.
Recruitment and drug selection
He added: “Last year, 2025-26, around 200 people were recruited into Alzheimer’s trials in the UK and in this trial alone we intend to recruit 1,200 people over the next four years.”
The AD-SMART (Alzheimer’s disease Systematic Multi-arm Adaptive Randomised Trial) study is being led by the UK Dementia Research Institute (UKDRI) and Alzheimer’s Research UK. Researchers said it would be the first multi-arm study to test drugs in a real-world population with dementia over a significant period of time.
It will be open to a wider group of patients than many drug trials which target only those with mild cognitive impairment or in the earliest stages of Alzheimer’s.
Atomoxetine was chosen because it targets the chemical noradrenaline, which regulates attention, memory and stress responses in the brain. Regions of the brain responsible for producing noradrenaline are known to be affected by Alzheimer’s disease.
Early research has also suggested that diabetic people taking metformin have a lower risk of developing dementia, which may be linked to its effects on inflammation and insulin resistance.
Funding and future prospects
Prof Malhotra said the two drugs selected were “undoubtedly cheaper” than treatments such as lecanemab and donanemab, which have been proven to slow progression of Alzheimer’s but rejected for NHS use on cost grounds. He added: “We very much hope that they will provide an alternative or perhaps a combination with whatever comes after lecanemab and donanemab.”
The first interim results are expected in around two and a half years, with full results due in late 2030. The trial is backed by £4.2million from the Medical Research Council and NIHR.
Prime Minister Andy Burnham, whose father Roy died with Alzheimer’s in September, said: "I know how it feels to lose a loved one to dementia and have seen first-hand the devastating impact this illness has on families."
Professor Siddharthan Chandran, director of the UKDRI, said it was a “very exciting time”, with major advances in both diagnostics and treatments for Alzheimer’s. But he warned that for too long, treatments have been tested in a “grossly inefficient way”. He added: "Because of the way SMART trials are designed, biotech and pharmaceutical companies can also bring their drugs straight into the trial."
Dr Sheona Scales, director of research at Alzheimer’s Research UK, said: "For people living with Alzheimer's disease, time is precious. We urgently need more treatment options that can help people live better for longer and stay connected to the people they love."
Patient perspective
Heather Ransome, 67, is among the first patients to join the AD-SMART study. She was diagnosed with Alzheimer’s in 2024. She said: "Before my diagnosis, my partner and I were going on lots of cruises and coach holidays, enjoying retirement together."
Heather, who lives in the Isle of Wight with her partner Roger, said joining the trial had given her “some hope for the future”. She added: "It’s not too taxing, just some extra tablets to take every day. I don’t know whether I’m being given the active treatment, but if it helps me, or helps others in future, that feels positive."
People with a confirmed Alzheimer’s diagnosis who would like to take part can register their interest by contacting the AD-SMART recruitment co-ordinator at adsmart@psych.ox.ac.uk or on 01865 283806. The Alzheimer’s Research UK Infoline is also available at infoline@alzheimersresearchuk.org or on 0300 111 5111.
