A drug used to treat type 2 diabetes may reduce the risk of dementia by 35%, according to a large study carried out by a team of scientists in Korea, who analysed data from more than 220 000 people.
The number of people with dementia globally is expected to nearly triple to 153m by 2050, while health and social costs linked to dementia already exceeding $1trn a year, research shows.
Type 2 diabetes is one of 14 risk factors associated with a greater risk of developing dementia, and the Korean study, published in The BMJ, suggests that a medicine used to treat type 2 diabetes, called sodium-glucose cotransporter-2 (SGLT-2) inhibitors, may lower this risk.
The Guardian reports that although previous studies have suggested SGLT-2 inhibitors could have a protective effect against dementia for older patients, until now, any protective effect on younger people and specific types of dementia, like Alzheimer’s and vascular dementia, has been unclear.
For the study, the academics – from Seoul National University Bundang Hospital – analysed data from more than 220 000 type 2 diabetics aged between 40 and 69 on the Korea national health insurance service who did not already have dementia.
Half were taking SGLT-2 inhibitors, which reduce the amount of glucose the kidneys reabsorb, and half were taking another drug called dipeptidyl peptidase 4 (DPP-4) inhibitors, which block the enzyme that helps increase insulin levels after food.
A total of 1 172 participants newly diagnosed with dementia were identified during the study period.
The researchers calculated SGLT-2 inhibitors were associated with a 35% lower risk of dementia compared with DPP-4 inhibitors.
They also identified a 39% reduced risk for Alzheimer’s disease and a 52% reduced risk for vascular dementia associated with patients taking SGLT-2 inhibitors.
The authors cautioned that this was an observational study and so could not prove cause and effect, but concluded that repurposing existing drugs to treat diseases that cause dementia “is one that has huge potential”, although further trials were needed to confirm their findings.
Dr Jacqui Hanley, head of research at Alzheimer’s Research UK, said the data were “promising”, adding: “People affected by dementia urgently need effective treatments.”
Repurposing medication that has already been licensed for treating dementia could speed up the process of testing them in clinical trials, as well as making it significantly cheaper, she said. “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.”
But Professor William Whiteley, the associate director of the British Heart Foundation data science centre, said: “If this study were true, then SGLT-2 inhibitors would almost halve the risk of some types of dementia, which is 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.”
Study details
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
Anna Shin, Bo Kyung Koo, Jun Young Lee, Eun Ha Kang.
Published in The BMJ on 4 July 2024
Abstract
Objective
To compare the risk of dementia associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors in adults aged 40-69 years with type 2 diabetes.
Design
Population based cohort study.
Setting
Korean National Health Insurance Service data, 2013-21.
Participants
A total of 110 885 propensity score matched pairs of adults with type 2 diabetes aged 40-69 years who were initiators of either an SGLT-2 inhibitor or a DPP-4 inhibitor.
Main outcome measures
The primary outcome was new onset dementia. Secondary outcomes were dementia requiring drug treatment and individual types of dementia, including Alzheimer’s disease and vascular dementia. Control outcomes were genital infections (positive), and osteoarthritis related clinical encounters and cataract surgery (negative). Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox models. Follow-up time stratified analyses (>2 years and ≤2 years) and subgroup analyses by age, sex, concomitant use of metformin, and baseline cardiovascular risk were performed.
Results
110 885 propensity score matched pairs of initiators of an SGLT-2 inhibitor or a DPP-4 inhibitor were followed-up for a mean 670 (standard deviation 650) days, generating 1172 people with newly diagnosed dementia: incidence rate 0.22 per 100 person years in initiators of SGLT-2 inhibitors and 0.35 per 100 person years in initiators of DPP-4 inhibitors, with hazard ratios of 0.65 (95% CI 0.58 to 0.73) for dementia, 0.54 (0.46 to 0.63) for dementia requiring drugs, 0.61 (0.53 to 0.69) for Alzheimer’s disease, and 0.48 (0.33 to 0.70) for vascular dementia. The hazard ratios for the control outcomes were 2.67 (2.57 to 2.77) for genital infections, 0.97 (0.95 to 0.98) for osteoarthritis related encounters, and 0.92 (0.89 to 0.96) for cataract surgery. When calibrated for residual confounding measured by cataract surgery, the hazard ratio for dementia was 0.70 (0.62 to 0.80). The association was greater for more than two years of treatment (hazard ratio of dementia 0.57, 95% CI 0.46 to 0.70) than for two years or less (0.52, 0.41 to 0.66) and persisted across subgroups.
Conclusion
SGLT-2 inhibitors might prevent dementia, providing greater benefits with longer treatment. As this study was observational and therefore prone to residual confounding and informative censoring, the effect size could have been overestimated. Randomised controlled trials are needed to confirm these findings.
See more from MedicalBrief archives:
Older diabetes drugs linked to lower dementia risk – US study
Some diabetes drugs may reduce the risk of Alzheimerʼs disease — Korea study
Alzheimer’s Society calls for 'failed' dementia drug trials to be revisited