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

Article type: Research Article

Authors: Low, Serena^{a; b; c} | Goh, Kiat Sern^d | Ng, Tze Pin^e | Moh, Angela^b | Ang, Su Fen^b | Wang, Jiexun^b | Ang, Keven^b | Tang, Wern Ee^f | Lim, Ziliang^f | Subramaniam, Tavintharan^a | Sum, Chee Fang^a | Lim, Su Chi^{a; b; c; g; *}

Affiliations: [a] Diabetes Centre, Admiralty Medical Centre, Singapore, Singapore | [b] Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore | [c] Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore | [d] Department of Geriatrics. Changi General Hospital, Singapore | [e] Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [f] National Healthcare Group Polyclinics, Singapore, Singapore | [g] Saw Swee Hock School of Public Health, National University of Singapore, Singapore

Correspondence: [*] Correspondence to: Associate Professor Su Chi Lim, Diabetes Centre, Admiralty Medical Centre, 676 Woodlands Drive 71, 730676, Singapore. Tel.: +65 6602353; E-mail: lim.su.chi@ktph.com.sg.

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.

Keywords: Cognitive function, sodium-glucose co-transporter-2 inhibitors, type 2 diabetes

DOI: 10.3233/JAD-215678

Journal: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 635-642, 2022