Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy

Summary

About 30% of persons with epilepsy have seizures that do not respond to drugs. The ketogenic diet is an effective treatment option for them, but this high fat diet is strict and difficult to maintain. The properties of gliflozins, which often are used to treat type 2 diabetes, make them a potential replacement for the ketogenic diet. This pilot study will determine whether gliflozins induce ketosis and could be used to treat adults with epilepsy safely.

Timeline

Start

2022-08-17

Primary completion

2023-03-01

Completion

2023-06-30

Publications

• Background Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology. 2003 Dec 23;61(12):1789-91. doi: 10.1212/01.wnl.0000098889.35155.72.
• Background Pfeifer HH, Thiele EA. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology. 2005 Dec 13;65(11):1810-2. doi: 10.1212/01.wnl.0000187071.24292.9e.
• Background Rho JM, Sankar R. The ketogenic diet in a pill: is this possible? Epilepsia. 2008 Nov;49 Suppl 8(Suppl 8):127-33. doi: 10.1111/j.1528-1167.2008.01857.x.
• Background Stafstrom CE, Roopra A, Sutula TP. Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG). Epilepsia. 2008 Nov;49 Suppl 8:97-100. doi: 10.1111/j.1528-1167.2008.01848.x.
• Background Stafstrom CE, Ockuly JC, Murphree L, Valley MT, Roopra A, Sutula TP. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol. 2009 Apr;65(4):435-47. doi: 10.1002/ana.21603.
• Background Ferrannini E, Baldi S, Frascerra S, Astiarraga B, Heise T, Bizzotto R, Mari A, Pieber TR, Muscelli E. Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes. 2016 May;65(5):1190-5. doi: 10.2337/db15-1356. Epub 2016 Feb 9.
• Background Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Cross JH, Dahlin MG, Donner EJ, Guzel O, Jehle RS, Klepper J, Kang HC, Lambrechts DA, Liu YMC, Nathan JK, Nordli DR Jr, Pfeifer HH, Rho JM, Scheffer IE, Sharma S, Stafstrom CE, Thiele EA, Turner Z, Vaccarezza MM, van der Louw EJTM, Veggiotti P, Wheless JW, Wirrell EC; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018 May 21;3(2):175-192. doi: 10.1002/epi4.12225. eCollection 2018 Jun.
• Background Biester T, Kordonouri O, Danne T. Beyond type 2 diabetes: sodium glucose co-transporter-inhibition in type 1 diabetes. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:53-61. doi: 10.1111/dom.13659.
• Background Kim SR, Lee SG, Kim SH, Kim JH, Choi E, Cho W, Rim JH, Hwang I, Lee CJ, Lee M, Oh CM, Jeon JY, Gee HY, Kim JH, Lee BW, Kang ES, Cha BS, Lee MS, Yu JW, Cho JW, Kim JS, Lee YH. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020 May 1;11(1):2127. doi: 10.1038/s41467-020-15983-6.

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