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Study reveals possible cognitive benefits of antidiabetic drugs
Last reviewed: 02.07.2025
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Researchers analysing the potential cognitive effects of antidiabetic drugs in the records of more than 1.5 million patients with type 2 diabetes (T2D) have found that the risks of dementia and Alzheimer's disease (AD) were significantly lower in patients treated with metformin and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with other antidiabetic drugs. Their findings are published in the American Journal of Preventive Medicine by Elsevier.
T2DM has become a critical health problem affecting approximately 530 million patients worldwide. Accumulating evidence shows that patients with T2DM have at least a 50% increased risk of cognitive impairment and dementia, which manifests as impairments in executive functions, memory, and attention. Dementia itself is also a major health problem affecting more than 40 million patients worldwide.
Lead investigator, PharmD Yeo Jin Choi, PharmD, from the Department of Pharmacy, College of Pharmacy, Department of Regulatory Science, Graduate School, and the Institute for Innovation in Regulatory Science (IRIS) at Kyung Hee University, Seoul, Korea, explains: “As the prevalence of diabetes and dementia continues to increase each year, and with mounting evidence indicating a strong correlation between diabetes and dementia, the need for comprehensive studies on the risk of dementia associated with antidiabetic treatments becomes increasingly urgent. Understanding the potential cognitive effects of antidiabetic drugs is important not only to optimize patient care, but also to inform regulatory decisions and clinical guidelines to prioritize patient safety and advance public health.”
The researchers searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE (PubMed), and Scopus from inception to March 2024 to identify observational studies investigating the incidence of dementia and AD in patients after starting antidiabetic drugs. The study included data from 1,565,245 patients from 16 studies. A Bayesian network meta-analysis was performed to determine the risk of dementia and AD associated with antidiabetic drugs, and evidence was synthesized to compare the risk of dementia and AD associated with six classes of antidiabetic drugs: DPP-4 inhibitors, metformin, SGLT-2 inhibitors, sulfonylureas, alpha-glucosidase inhibitors, and thiazolidinediones.
Previous studies have suggested an increased risk of dementia with the use of antidiabetic drugs, particularly with agents with a high risk of hypoglycemia such as sulfonylureas and alpha-glucosidase inhibitors. Data on the risk of dementia associated with SGLT-2 inhibitors were limited prior to this study.
The lowest risk of dementia and AD in this new study was found in patients taking metformin. In addition, SGLT-2 inhibitors, which include Farxiga® and Jardiance®, were associated with a lower risk of dementia and AD, as well as cardiovascular benefits.
The risk of dementia associated with SGLT-2 inhibitors was similar to other antidiabetic drugs in patients younger than 75 years. However, the risk of dementia was significantly higher with DPP4 inhibitors, metformin, sulfonylureas, and thiazolidinediones (TZDs) compared with SGLT-2 inhibitors in patients aged 75 years and older. The risk of dementia was also significantly lower with SGLT-2 inhibitors compared with sulfonylureas in women.
The researchers note that the risks of dementia and AD associated with second- or third-line antidiabetic drugs, including GLP-1 agonists and insulin, were not assessed in this study.
This study contributes to a more comprehensive understanding of diabetes management by highlighting the importance of considering both metabolic and cognitive outcomes in clinical practice. It highlights the importance of individualized approaches to diabetes care, taking into account patient-specific factors such as age, gender, complications, body mass index (BMI), glycated hemoglobin (A1C), which measures blood glucose levels over the past three months, and cognitive health status, informing healthcare professionals in their decision-making when selecting appropriate treatment options for patients with diabetes.
Yeo Jin Choi concludes: “We were quite surprised by the study results, especially the potential cognitive benefits of SGLT-2 inhibitors compared with metformin and DPP-4 inhibitors in patients aged 75 years and older. This finding is particularly important given that SGLT-2 inhibitors are currently used to manage heart failure. Our study contributes to the existing evidence by suggesting potential additional benefits of SGLT-2 inhibitors in reducing the risk of dementia, which has significant clinical implications for diabetes management. Older patients aged 75 years and older may particularly benefit from these findings, as they often face greater cognitive health challenges.”