Association Between Use of Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors and Cognitive Function in a Longitudinal Study of Patients with Type 2 Diabetes

Abstract

Background: The association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) use and cognitive function in type 2 diabetes remains unclear. Objective: Explore the association between SGLT2i and longitudinal changes in cognitive function in adults with type 2 diabetes (T2DM) and assessed the cognitive domains which were impacted by SGLT2i. Methods: We conducted a prospective cohort study of 476 patients aged 60.6±7.4 years with follow-up period up to 6.4 years. Data on SGLT2i use was derived from questionnaire and verified with clinical database. We used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognition. The association between SGLT2i use and rate of RBANS score change was examined using multiple linear regression. Results: There were 138 patients (29.0%) on SGLT2i, including 84 (17.7%) for < 3 years and 54 (11.3%) for ≥3 years. SGLT2i use was positively associated with RBANS total score increase in language (coefficient 0.60; 95% CI 0.10–1.11; p = 0.019) in unadjusted analysis. This positive association persisted in fully adjusted model (coefficient 0.74; 95% CI 0.12 to 1.36; p = 0.019). SGLT2i use for ≥3 years was positively associated with RBANS score increase globally and in language domain in fully adjusted analysis with coefficients 0.54 (95% CI 0.13 to 0.95; p = 0.010) and 1.12 (95% CI 0.27 to 1.97; p = 0.010) respectively. Conclusion: Our findings revealed a previously unobserved association between ≥3 years SGLT2i use and improved cognitive scores globally and in language domain and executive function. Future studies should investigate the role of SGLT2i in ameliorating cognitive decline.

Association between diabetes mellitus and post‐stroke cognitive impairment

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“…Carmen et al found that empagliflozin reduced vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes (48). However, we have little information on how SGLT2 inhibitors affect cognitive decline in clinical diabetes (49). Serena et al found that a SGLT2 inhibitor was positively associated with better cognitive scores in a cohort of patients with diabetes (50).…”

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“…And a prospective study shows significant beneficial effects of the EMP on cognitive in frail older adults with diabetes (Mone et al, 2022). In addition, SGLT2I's ≥ 3 years use is related to the improvement of cognitive scores (Low et al, 2022). According to the existing evidence, longterm use of SGLT2i can improve cognitive function, especially for elderly diabetics.…”

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