Association of Metformin use with risk of dementia in patients with type 2 diabetes: A systematic review and meta-analysis

Aim: There is ongoing debate concerning the association of metformin with the risk of dementia in type 2 diabetes mellitus (T2DM). This study was conducted to evaluate the impact of metformin therapy on dementia in patients with T2DM. Materials and methods: PubMed, Embase, Cochrane Library, Web of Science and the ClinicalTrials.gov website were searched until 9 April 2024. Cohort studies investigating the effects of metformin therapy compared with other antidiabetic drugs or no therapy in T2DM were included. The hazard ratio (HR) and the 95% confidence interval (CI) were computed using the random effects model. Results: Twenty cohort studies (24 individual comparisons) involving 3 463 100 participants were identified. A meta-analysis revealed that people with T2DM who take metformin are linked to a lower incidence of all-cause dementia compared to non-user (n = 17, HR = 0.76, 95% CI = 0.65-0.91, p = 0.002, I-2 = 98.9%) and sulfonylureas (n = 5, HR = 0.88, 95% CI = 0.85-0.90, p < 0.001, I-2 = 9.7%), but not to thiazolidinedione (n = 2, HR = 0.53, 95% CI = 0.08-3.41, p = 0.503, I-2 = 92.7%). Additionally, metformin showed favourable effects in non-specified T2DM (n = 19, HR = 0.75, 95% CI = 0.64-0.89), but not in newly diagnosed T2DM (n = 5, HR = 1.01, 95% CI = 0.81-1.27). Conclusion:<bold> </bold>Metformin might correlate with a lower dementia incidence in people with T2DM. However, it is crucial to interpret these results with caution considering the high heterogeneity.