THE EFFECT OF SGLT2 INHIBITORS ON COGNITIVE FUNCTION IN PATIENTS WITH TYPE 2 DIABETES
Keywords:
SGLT2i, type 2 diabetes, cognitive impairment (CI), dementia, neuroprotectionAbstract
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of developing cognitive impairments, including dementia. In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have gained popularity as antidiabetic agents with potential neuroprotective effects. SGLT2 inhibitors have demonstrated potential benefits beyond improving cardiac and renal function, particularly in the prevention and treatment of cognitive impairments (CI), including mild cognitive impairment, Alzheimer’s disease, and vascular dementia in patients with T2DM. Research suggests that SGLT2i may improve diabetic-related cognitive impairments through mechanisms involving metabolism, inflammation, oxidative stress, neurotrophic factors, and acetylcholinesterase (AChE) inhibition. This article is dedicated to analyzing the data on the impact of SGLT2 inhibitors on cognitive function in patients with T2DM. The literature review highlights the potential of these agents in reducing the risk of neurodegeneration and stabilizing cognitive status; however, further large-scale clinical studies are needed.
References
Biessels G.J., Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. 2018;14(10):591–604.
Cherney D.Z.I., Cooper M.E. The role of SGLT2 inhibitors in modifying neurocognitive decline in diabetes. Diabetologia. 2020;63(11):2246– 2250.
Tanaka A. et al. SGLT2 inhibitors and risk of dementia in patients with type 2 diabetes: A real-world data analysis. Diabetes Care. 2023;46(2):348–355.
Kodl C.T., Seaquist E.R. Cognitive dysfunction and diabetes mellitus. Endocr Rev. 2008;29(4):494–511.
Vallon V., Thomson S.C. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60(2):215–225.
Rosenstock J. et al. Effects of empagliflozin on brain health: subanalysis of a randomized clinical trial. Lancet Neurology. 2021;20(5):389–397.
Garcia-Ropero A. et al. Cognitive benefits of dapagliflozin in elderly patients with type 2 diabetes and cardiovascular risk. Front Aging Neurosci. 2022;14:813345.
Sachdev P.S., Blacker D., Blazer D.G., Ganguli M., Jeste D.V., Paulsen J.S., Petersen R.C. Classifying neurocognitive disorders: The DSM-5 approach. Nat. Rev. Neurol. 2014;10:634–642. doi: 10.1038/nrneurol.2014.181.
Ott A., Stolk R.P., Hofman A., van Harskamp F., Grobbee D.E., Breteler M.M. Association of diabetes mellitus and dementia: The Rotterdam Study. Diabetologia. 1996;39:1392–1397.
Mukadam N., Wolters F.J., Walsh S., Wallace L., Brayne C., Matthews F.E., Sacuiu S., Skoog I., Seshadri S., Beiser A., et al. Changes in prevalence and incidence of dementia and risk factors for dementia: An analysis from cohort studies. Lancet Public Health. 2024;9:e443–e460.
Chekol Tassew W., Ferede Y.A., Zeleke A.M. Cognitive impairment and associated factors among patients with diabetes mellitus in Africa: A systematic review and meta-analysis. Front. Endocrinol. 2024;15:1386600.
Kuate Defo A., Bakula V., Pisaturo A., Labos C., Wing S.S., Daskalopoulou S.S. Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta-analysis. Diabetes Obes. Metab. 2024;26:441–462.
Chen Q., Zhu S., Shang J., Fang Q., Xue Q., Hua J. Trends in Cognitive Function Before and After Diabetes Onset: The China Health and Retirement Longitudinal Study. Neurology. 2024;102:e209165.
