In:
Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 80, No. 3 ( 2024-09), p. 633-648
Abstract:
No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. Approach and Results: Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score–matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70–0.98, p =0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60–0.90, p =0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79–0.97, p =0.01), and this difference remained significant (adjusted hazard ratio=0.72–0.89, all p 〈 0.05) across various sensitivity analyses. Conclusions: Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.
Type of Medium:
Online Resource
ISSN:
0270-9139
DOI:
10.1097/HEP.0000000000000837
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2024
detail.hit.zdb_id:
1472120-X
