Metformin and SGLT2 inhibitors show lower dementia and Alzheimer’s risks than other antidiabetic treatments

A large retrospective analysis of the cognitive effects of various antidiabetic treatments has disclosed that the risks of dementia and Alzheimer’s disease (AD) were significantly lower in patients treated with metformin and sodium glucose co-transporter-2 inhibitors (SGLT-2i) compared to other antidiabetic drugs.

Their results appeared on July 11, 2024 in the American Journal of Preventive Medicine.

“Our study contributes to the existing evidence by suggesting potential additional benefits of SGLT-2 inhibitors in mitigating dementia risk, thereby providing significant clinical implications for diabetes management,” said lead investigator Yeo Jin Choi, PharmD, PhD, Department of Pharmacy, College of Pharmacy; Department of Regulatory Science, Graduate School; and Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Korea.

As background, the authors noted, “Dementia risk is substantially elevated in patients with diabetes. However, evidence on dementia risk associated with various antidiabetic regimens is still limited. This study aims to comprehensively investigate the risk of dementia and Alzheimer’s disease (AD) associated with various antidiabetic classes.

Data from 1,565,245 subjects from 16 studies were included in the analysis. The researchers used standard statistical tools to identify and quantify the risk of dementia and Alzheimer’s disease associated with the use of antidiabetics. They compared the risk of dementia and AD associated with six antidiabetic drug classes: DPP4 inhibitors, metformin, SGLT-2 inhibitors, sulfonylureas, alpha-glucosidase inhibitors, and thiazolidinediones.

They reported that risks of dementia and AD risks were significantly lower with metformin and sodium glucose co-transporter-2 inhibitors (SGLT2i), which include Farxiga® and Jardiance®.

Subjects treated with metformin showed the lowest risk of dementia, and those treated with α-glucosidase inhibitors showed the highest risk.

Choi said, “Elderly patients aged 75 years or older may particularly benefit from these findings, since they often face greater cognitive health concerns.”

The authors noted that dementia and AD risks associated with second- or third-line antidiabetics, including GLP-1 agonists and insulin, were not evaluated in the study.

They concluded, “Metformin and SGLT2i demonstrated lower dementia risk than other antidiabetic classes. Patient-specific factors may affect this relationship and cautious interpretation is warranted as metformin is typically initiated at an earlier stage with fewer complications. Hence, further large-scaled clinical trials are required.”