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Some diabetes drugs may reduce the risk of Alzheimerʼs disease — Korea study

A Korean study has found that people taking certain drugs to lower blood sugar for type 2 diabetes had less amyloid in the brain, a biomarker of Alzheimer's disease, when compared with both people with type 2 diabetes not taking the drugs and people without diabetes.

The research, published in the 11 August online issue of Neurology, the medical journal of the American Academy of Neurology, also found people taking these drugs, called dipeptidyl peptidase-4 inhibitors, showed slower cognitive decline than people in the other two groups.

In people with type 2 diabetes, the body no longer efficiently uses insulin to control blood sugar. Dipeptidyl peptidase-4 inhibitors, also known as gliptins, can be prescribed when other diabetes drugs do not work. They help control blood sugar when combined with diet and exercise.

"People with diabetes have been shown to have a higher risk of Alzheimer's disease, possibly due to high blood sugar levels, which have been linked to the build-up of amyloid beta in the brain," said study author Dr Phil Hyu Lee of Yonsei University College of Medicine in Seoul, South Korea. "Not only did our study show that people taking dipeptidyl peptidase-4 inhibitors to lower blood sugar levels had less amyloid in their brains overall, it also showed lower levels in areas of the brain involved in Alzheimer's disease."

The study involved 282 people with an average age of 76 who were followed up to six years. All had been diagnosed either with pre-clinical, early or probable Alzheimer's disease. Of the group, 70 people had diabetes and were being treated with dipeptidyl peptidase-4 inhibitors, 71 had diabetes but were not being treated with the drugs and 141 did not have diabetes. Those without diabetes were matched to those with diabetes for age, sex, and education levels. All had similar scores on cognitive tests at the start of the study.

Participants had brain scans to measure the amount of amyloid in the brain. Researchers found that those with diabetes who took the drugs had lower average amounts of amyloid plaques in the brain compared with those with diabetes who did not take the drugs and compared with the people who did not have diabetes.

All participants took a common thinking and memory test called the Mini-Mental State Exam (MMSE) on average, every 12 months for 2.5 years. Questions include asking a person to count backward from 100 by sevens or copying a picture on a piece of paper. Scores on the test range from zero to 30.

Researchers found that people with diabetes who took the drugs had an average annual decline of 0.87 points on their MMSE score, while people with diabetes who did not take the drugs had an average annual decline of 1.65 points. People without diabetes scored an average annual decline of 1.48 points.

When researchers adjusted for other factors that could affect test scores, they found that the scores of the people taking the drug declined by 0.77 points per year more slowly than the people who did not take the drug.

"Our results showing less amyloid in the brains of people taking these medications and less cognitive decline compared with people without diabetes raises the possibility that these medications may also be beneficial for people without diabetes who have thinking and memory problems," said Lee. "More research is needed to demonstrate whether these drugs may have neuroprotective properties in all people."

A limitation of the study was that data were not available to show the accumulation of amyloid in participants' brains over time. This study does not show cause and effect. It only shows an association.

The study was supported by the Korean Healthy Industry Development Institute and the Korean Ministry of Health & Welfare.

Study details

Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Diabetic Patients With AD-Related Cognitive Impairment

Seong Ho Jeong, Hye Ryun Kim, Jeonghun Kim, Hankyeol Kim, Namki Hong, Jin Ho Jung, Kyoungwon Baik, Hanna Cho,Chul Hyoung Lyoo, Byoung Seok Ye, Young H. Sohn, Joon-Kyung Seong, Phil Hyu Lee

Published in Neurology 11 August 2021


To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer’s disease-related cognitive impairment (ADCI).

We retrospectively reviewed 282 patients with ADCI who had positive scan of F-florbetaben amyloid: PET images were classified into three groups according to a prior diagnosis of diabetes and DPP-4i use: diabetic patients being treated with (ADCI-DPP-4i+, n=70) or without DPP-4i (ADCI-DPP-4i-, n=71), and non-diabetic patients (n=141). Multiple linear regression analyses were performed to determine inter-group differences in global and regional amyloid retention using standardised uptake value ratios calculated from cortical areas. We assessed the longitudinal changes in Mini-Mental State Examination (MMSE) score using a linear mixed model.

The ADCI-DPP-4i+ group had lower global amyloid burden than the ADCI-DPP-4i− group (β = 0.075, SE = 0.024, p = 0.002) and the non-diabetic ADCI group (β = 0.054, SE = 0.021, p = 0.010) after adjusting for age, sex, education, cognitive status, and APOE ε4 carrier status. Additionally, the ADCI-DPP-4i+ group had lower regional amyloid burden in temporo-parietal areas than either the ADCI-DPP-4i− group or the non-diabetic ADCI group. The ADCI-DPP-4i+ group showed a slower longitudinal decrease in MMSE score (β = 0.772, SE = 0.272, p = 0.005) and memory recall sub-score (β = 0.291, SE = 0.116, p = 0.012) than the ADCI-DPP-4i− group.

These findings suggest that DPP-4i use is associated with low amyloid burden and favourable long-term cognitive outcome in diabetic patients with ADCI.


Neurology Journal article – Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Diabetic Patients With AD-Related Cognitive Impairment (Open access)


See more from MedicalBrief archives:


Defining the diabetes and dementia connection


Purified resveratrol may stabilise Alzheimer’s


Cognitive performance impacted by insulin resistance



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