August 28, 2024

expert reaction to observational study claiming certain diabetes drugs might prevent dementia

A study published in The BMJ looks at the association between certain diabetes drugs and lower risk of developing dementia. 

Professor Tara Spires-Jones, Deputy Director, Centre for Discovery Brain Sciences and Group Leader at the UK Dementia Research Institute, University of Edinburgh, said:

“This paper by Shin and colleagues represents a well-conducted study looking at data from over 200,000 people. The scientists observed that a Sodium-glucose cotransporter-2 (SGLT-2) inhibitor drug used to treat diabetes is associated with lower risk of developing dementia. Further research using controlled trials is needed to confirm these results.

“This study adds to substantial data from around the world linking diabetes to dementia risk and to a growing body of evidence suggesting that treating conditions like diabetes can lower the risk of developing dementia. Future research is needed to understand how these treatments protect the brain from developing diseases that cause dementia.”

Dr Ivan Koychev, Senior Clinical Researcher, Dementia Platform UK, University of Oxford, said:

“The results add to existing strong epidemiological evidence for dementia risk reduction through diabetes medications, namely SGLT2-inhibitors and glucagon-like peptide-1 receptor agonists. As in the current study, the risk of developing dementia is reduced substantially (30-40%). The mechanism through which these effects take place are unknown but likely relate to either affecting inflammation in the brain, reducing the risk for cerebrovascular events or modulating glucose metabolism in the brain. The caveat, as in previous epidemiological studies, is that it is not possible to draw causal links from such study designs. However, they strengthen the case for testing in clinical trial settings these types of drugs in people at risk for dementia. The great advantage of this so-called repurposing approach (i.e. using an existing drug in a new indication) is that it reduces greatly the risk of the drug failing through safety concerns as they are already used in everyday clinical practice.”

Dr Jacqui Hanley, Head of Research at Alzheimer’s Research UK, said:

“People affected by dementia urgently need effective treatments, as last week’s news of Alzheimer’s drug lecanemab’s rejection by NICE emphasised.

“Research – including the recent Lancet Commission report – has highlighted the link between diabetes and an increased risk of dementia. This has led to renewed focus on the possibility that diabetes drugs might reduce this added dementia risk.

“This large study followed people with diabetes who were already taking two different diabetes drugs called sodium-glucose cotransporter (SGLT-2) inhibitors and dipeptidyl peptidase-4 inhibitors, to see if there were differences in whether they went on to be diagnosed with dementia. Its key finding that one of these drugs, SGLT-2 inhibitors, appears to be linked to a lower dementia risk, is promising and now needs to be confirmed in robust clinical trials. It will also be important to investigate the mechanisms behind this apparent effect, as this could give researchers clues for other treatment approaches.

“It is encouraging to see large studies exploring whether drugs that have already been licensed could be repurposed as dementia treatments. Since these drugs have already been shown to be safe for use in people, this could potentially speed up the process of testing them in clinical trials against dementia, as well as making it significantly cheaper.

“More broadly, the idea of repurposing existing drugs to treat the diseases that cause dementia is one that has huge potential. At Alzheimer’s Research UK, we know that roughly a third of drugs in clinical trials for Alzheimer’s disease are already used for other conditions. If we are to cure dementia, clinicians will need a toolkit of treatments which tackle different aspects of the disease and can be used in combination. Research into repurposing drugs may help us do just that.”

Professor William Whiteley, Associate Director, BHF Data Science Centre, HDRUK; Clinical Lead, Scottish Stroke Research Network, CSO; Professor of Neurology and Epidemiology, University of Edinburgh, said:

“People with diabetes have a higher risk of dementia, so finding medicines to reduce this risk is important.

“Unfortunately, one can never be sure about the effects of a medicine by looking at health record data. 

“If this study were true, then SGLT-2 inhibitors would almost halve the risk of some types of dementia, which is a much larger than the effect of medicines to reduce dementia progression, or medicines to prevent heart attack and stroke. Instead, a quirk of the study design has probably given this result. 

“There are ongoing randomised trials of some diabetes medicines for dementia progression. The results of these trials will give more reliable answers.

“The authors have interpreted their results cautiously.”

‘Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study’ by Anna Shin et al. was published in The BMJ at 23:30 hours UK time (BST) Wednesday 28 August.

DOI: 10.1136/bmj.q1841

Declared interests

Prof Spires-Jones: I have no conflicts with this study but have received payments for consulting , scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Esai. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.

Dr Koychev: Ivan Koychev has received a grant to conduct a study of semaglutide in dementia and speaker fees from Novo Nordisk. He is a paid medical advisor for digital healthcare (Five Lives SAS, Cognes, Cognetivity, Lola Speaks) and biotechnology (CFDX Ltd) companies in the dementia space.

Dr Hanley: No COIs.

Prof Whiteley: Eisai (a drugs company that make a dementia drug) partially funds Neurii (a collaboration between Eisai, Gates, LifeArc, University of Edinburgh and HDRUK) which funds a research project I lead. 

I am an independent expert witness to UK courts.

I am employed by University of Edinburgh, with support from the Scottish Government and the BHF Data Science Centre, HDRUK.