Meta-Analysis Links Metformin to Lower Dementia Risk in T2D

TOPLINE:

Patients with type 2 diabetes (T2D) on metformin face a lower risk for all-cause dementia than those not on metformin, with the protective effect being particularly evident in patients with nonspecified diabetes.

METHODOLOGY:

• Multiple meta-analyses have shown that metformin has neuroprotective and neuromodulatory functions in T2D, but they relied heavily on earlier studies with methodological limitations.
• Researchers conducted an updated meta-analysis by searching published literature across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases until April 9, 2024, to investigate the impact of metformin therapy on dementia risk in patients with T2D.
• The literature search was restricted to English-language studies, and case-control studies were excluded due to their higher risk for bias.
• The analysis utilized hazard ratios (HRs) computed using the random effects model to evaluate the risk for dementia.

TAKEAWAY:

• Researchers included 20 cohort studies comparing patients with T2D who received either metformin therapy (n = 2,044,866) or other antidiabetic drugs or no therapy (n = 1,418,234), with median follow-up durations ranging from 3 months to 12.4 years.
• Metformin use was linked to a lower incidence of dementia in 24 comparisons from 20 studies (HR, 0.79; P P = .002) and sulfonylureas users (HR, 0.88; P
• Metformin use was associated with a decreased risk for dementia in patients with nonspecified T2D in 19 comparisons (HR, 0.75; P P = .900).
• Sex subgroup analysis of four comparisons indicated a lower risk for dementia with metformin use in both men (HR, 0.86; P P = .002).
• Metformin use was associated with a reduced risk for non-Alzheimer’s dementia (HR, 0.58; P P = .816) or vascular dementia (P = .610) in eight and seven comparisons, respectively.

IN PRACTICE:

“Due to the high heterogeneity observed in the included studies and the small number of studies in specific subgroups, more prospective cohort studies and [randomized clinical trials] are needed in the future to evaluate the association between metformin and the risk of dementia in patients with [T2D],” the authors wrote.

SOURCE:

The study was led by Chunbian Tang, MD, Medical School of Tianjin University, Tianjin, China. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS:

Significant heterogeneity existed among the included studies due to variations in population characteristics, treatment exposures, study designs, and statistical methods. The analysis was primarily based on retrospective studies, potentially limiting generalizability. The comparison focused only on metformin vs sulfonylureas and thiazolidinedione, and comparisons with newer drugs that may have better neuroprotective properties, such as sodium- glucose transporter 2 inhibitor and glucagon-like peptide 1 receptor agonists, were not performed. 

DISCLOSURES:

The study received support from the Science and Technology Project of the Binhai New Area Health Committee and Research Innovation and Translation Fund of Tianjin Fifth Central Hospital. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.