A class of drugs used to treat type 2 diabetes have been shown to be associated with a reduced risk of dementia, say researchers.

Analysis of a large database of people aged 40-69 with type 2 diabetes found a 35% reduced risk of dementia associated with use of sodium-glucose cotransporter-2 (SGLT2) compared with dipeptidyl peptidase-DPP-4 inhibitors.

The effect size could have been overestimated, the researchers wrote in the BMJ, but the association is significant enough to warrant a randomised controlled trial, they concluded.

It is not the first study to note a reduced risk of dementia associated with SGLT2 inhibitors but previous research had found the link in older people.

The analysis of data from the Korea National Health Insurance Service compared 110,885 matched pairs of adults with no dementia diagnosis and taking either a SGLT2 inhibitor or a DPP-4 inhibitor between 2013 and 2021.

The most common index SGLT2 inhibitor was dapagliflozin (58.6%), followed by empagliflozin (35.4%).

Over the average follow-up period of 670 days, 1,172 participants with newly diagnosed dementia were identified.

Dementia rates per 100 person years were found to be 0.22 for those using SGLT2 inhibitors and 0.35 for those using DPP-4 inhibitors, the researchers reported.

When looking at types of dementia, they found a 39% reduced risk for Alzheimer’s disease, and a 52% reduced risk for vascular dementia associated with SGLT2 inhibitors compared with DPP-4 inhibitors.

They also noted that link with SGLT-2 inhibitors seemed to be more pronounced with longer treatment duration with a 48% reduced risk of dementia for more than two years of treatment versus a 43% reduced risk for two years or less.

Information on some factors such as smoking and alcohol consumption and duration of type 2 diabetes were not fully available, the researchers pointed out.

But the results in this younger group were highly consistent across subgroups, they said.

As well as confirming the result, more research is needed ‘to explore the underlying mechanisms of any neuroprotective effects of SGLT2 inhibitors’, the team concluded.

SGLT2 inhibitors are also recommended by NICE for treatment of heart failure and chronic kidney disease.

Professor Tara Spires-Jones, group leader at the UK Dementia Research Institute at the University of Edinburgh, said: ‘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.’

This article was first published by our sister title Pulse