New research reveals that certain antidiabetic drugs may lower the risk of dementia and Alzheimer’s disease, particularly in older patients.
A recent study published in the American Journal of Preventive Medicine has highlighted the potential cognitive benefits of antidiabetic drugs, including metformin, for patients with type 2 diabetes. The study, which involved a comprehensive analysis of over 1.5 million patient records, suggests that these medications may play a role in mitigating the risk of dementia, including Alzheimer’s disease.
Longevity.Technology: With the prevalence of both diabetes and dementia steadily increasing worldwide, the study’s findings are particularly significant. Type 2 diabetes is now a major global health concern, affecting approximately 483 million individuals [1]; dementia, in its various forms, impacts over 55 million people [2]. As these diseases are both strongly correlated with aging, the burden on healthcare systems dealing with aging populations is set to rise substantially. Research linking diabetes with cognitive decline has been growing, as patients with type 2 diabetes are known to have a 50% higher risk of cognitive impairment, which manifests in difficulties with executive function, memory and attention.
Earlier studies had raised concerns about the potential cognitive risks associated with certain antidiabetic drugs [3], particularly those with a higher risk of causing hypoglycemia, such as sulfonylureas and alpha-glucosidase inhibitors. These studies suggested that the use of these drugs could increase the likelihood of developing dementia. Given the high rate of comorbidity between diabetes and cognitive decline, the new findings that highlight cognitive benefits of specific antidiabetic treatments provide a more encouraging outlook for patient care.
The investigators, led by Dr Yeo Jin Choi of Kyung Hee University in Seoul, South Korea, performed a Bayesian network meta-analysis on data from 16 observational studies, including 1,565,245 patients. Their aim was to assess the relative dementia and Alzheimer’s risks associated with six different classes of antidiabetic drugs: DPP-4 inhibitors, metformin, SGLT-2 inhibitors, sulfonylureas, alpha-glucosidase inhibitors and thiazolidinediones. The results showed that metformin and SGLT-2 inhibitors were associated with a significantly lower risk of dementia compared with the other drugs analyzed [4].
Choi explained the importance of this research, particularly in the context of the growing incidence of both diabetes and dementia. “As the prevalence of both diabetes and dementia continues to rise each year, and with mounting evidence suggesting a strong correlation between diabetes and dementia, the need for comprehensive research in dementia risk associated with antidiabetic treatment becomes increasingly imperative,” she said [5]. Her team’s research highlights the importance of considering the cognitive effects of antidiabetic medications in order to inform both patient care and regulatory decisions.
The findings concerning metformin were particularly noteworthy. Widely prescribed as a first-line treatment for type 2 diabetes, and with a global market estimated to reach more than US$6,420 billion by 2030 [6], metformin was shown to have the lowest overall risk of dementia and Alzheimer’s disease among the drugs studied [4]. This suggests that metformin may confer cognitive protective benefits beyond its known effects on blood sugar control. The study also pointed to potential benefits associated with SGLT-2 inhibitors, which have been primarily used to manage heart failure and reduce cardiovascular risk but are now showing promise in reducing dementia risk, particularly in older populations.
One of the study’s key observations was that SGLT-2 inhibitors, including drugs such as Farxiga and Jardiance, showed a notably lower risk of dementia in patients aged 75 years or older. In contrast, dipeptidyl peptidase-4 inhibitors (DPP-4i), metformin, sulfonylureas and thiazolidinediones were all associated with higher dementia risks in this age group [4]. This distinction is particularly relevant given the greater cognitive concerns that often accompany aging; it suggests that SGLT-2 inhibitors may hold a particular advantage for elderly patients with type 2 diabetes, a demographic that frequently faces multiple health challenges.
Interestingly, while metformin had the lowest dementia risk across most groups, SGLT-2 inhibitors outperformed metformin in individuals over 75 [4], suggesting that age may play a significant role in how different antidiabetic drugs affect cognitive health. The reasons for these differences are not yet fully understood, and the study authors wisely urge caution in interpreting the results. As Choi noted: “We were quite surprised by the study results, particularly the potential cognitive benefits of SGLT-2 inhibitors over metformin and DPP-4 inhibitors in patients aged 75 years or older [5].”
The analysis also demonstrates the importance of individualized treatment in diabetes management – factors such as patient age, sex, existing complications, body mass index (BMI), and cognitive health status must be carefully considered when prescribing antidiabetic drugs. As dementia risks appear to vary across different antidiabetic classes and patient profiles, personalized care becomes crucial in ensuring optimal outcomes for both metabolic and cognitive health.
It is important to note that the study did not examine all types of antidiabetic medications. Second- or third-line therapies, such as GLP-1 agonists and insulin, were not included in the analysis, leaving some questions about the cognitive effects of these treatments unanswered. Further research, including large-scale clinical trials, will be needed to build on these findings and explore the full scope of how antidiabetic drugs influence cognitive outcomes.
[1] https://idf.org/about-diabetes/diabetes-facts-figures/
[2] https://www.who.int/news-room/fact-sheets/detail/dementia
[3] https://diabetesjournals.org/care/article/36/10/2981/30476/Increased-Risk-of-Cognitive-Impairment-in-Patients
[4] https://www.ajpmonline.org/article/S0749-3797(24)00140-5/abstract
[5] https://www.elsevier.com/about/press-releases/metformin-and-other-antidiabetic-drugs-can-help-reduce-the-risk-of-dementia-in-patients-with-type-2-diabetes
[6] https://www.databridgemarketresearch.com/reports/global-metformin-market
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