Mendelian randomisation reveals Sodium-glucose Cotransporter-1 inhibition's potential in reducing Non-Alcoholic Fatty Liver Disease risk

Dobbie, Laurence J ORCID: 0000-0003-1908-848X, Cuthbertson, Daniel J ORCID: 0000-0002-6128-0822, Hydes, Theresa J ORCID: 0000-0002-7768-6886, Alam, Uazman ORCID: 0000-0002-3190-1122 and Zhao, Sizheng Steven (2023) Mendelian randomisation reveals Sodium-glucose Cotransporter-1 inhibition's potential in reducing Non-Alcoholic Fatty Liver Disease risk. EUROPEAN JOURNAL OF ENDOCRINOLOGY, 188 (6). K33-K37.

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Official URL: http://dx.doi.org/10.1093/ejendo/lvad068

Abstract

Non-alcoholic fatty liver disease (NAFLD) has no approved pharmacological treatments. Sodium-glucose cotransporter (SGLT)-1 is a glucose transporter that mediates small intestinal glucose absorption. We evaluated the impact of genetically proxied SGLT-1 inhibition (SGLT-1i) on serum liver transaminases and NAFLD risk. We used a missense variant, rs17683430, in the SLC5A1 gene (encoding SGLT1) associated with HbA1c in a genome-wide association study (n = 344 182) to proxy SGLT-1i. Outcome genetic data comprised 1483 NAFLD cases and 17 781 controls. Genetically proxied SGLT-1i was associated with reduced NAFLD risk (OR 0.36; 95%CI 0.15, 0.87; P = .023) per 1 mmol/mol HbA1c reduction, and with reductions in liver enzymes (alanine transaminase, aspartate transaminase, gamma-glutamyl transferase). Genetically proxied HbA1c, not specifically via SGLT-1i, was not associated with NAFLD risk. Colocalisation did not demonstrate genetic confounding. Overall, genetically proxied SGLT-1i is associated with improved liver health, this may be underpinned by SGLT-1-specific mechanisms. Clinical trials should evaluate the impact of SGLT-1/2 inhibitors on the prevention and treatment of NAFLD.

Item Type:	Article
Uncontrolled Keywords:	sodium-glucose cotransporter, NAFLD, liver transaminases, SGLT1, glycated hemoglobin, type 2 diabetes
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	13 Oct 2023 13:38
Last Modified:	13 Oct 2023 13:38
DOI:	10.1093/ejendo/lvad068
Open Access URL:	https://doi.org/10.1093/ejendo/lvad068
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3173698