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Inhibition of sodium-glucose cotransporter-2 and liver-related complications in individuals with diabetes: a Mendelian randomization and population-based cohort study.
Chung, Sung Won; Moon, Hye-Sung; Shin, Hyunjae; Han, Hyein; Park, Sehoon; Cho, Heejin; Park, Jeayeon; Hur, Moon Haeng; Park, Min Kyung; Won, Sung-Ho; Lee, Yun Bin; Cho, Eun Ju; Yu, Su Jong; Kim, Dong Ki; Yoon, Jung-Hwan; Lee, Jeong-Hoon; Kim, Yoon Jun.
Affiliation
  • Chung SW; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Moon HS; Division of Gastroenterology, Liver Center, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Shin H; RexSoft Inc., Seoul, South Korea.
  • Han H; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Park S; Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, South Korea.
  • Cho H; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
  • Park J; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Hur MH; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Park MK; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Won SH; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Lee YB; RexSoft Inc., Seoul, South Korea.
  • Cho EJ; Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, South Korea.
  • Yu SJ; Interdisciplinary Program for Bioinformatics, College of Natural Science, Seoul National University, Seoul, South Korea.
  • Kim DK; Institute of Health and Environment, Seoul National University, Seoul, South Korea.
  • Yoon JH; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Lee JH; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
  • Kim YJ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Hepatology ; 80(3): 633-648, 2024 Sep 01.
Article in En | MEDLINE | ID: mdl-38466796
ABSTRACT
BACKGROUND AND

AIMS:

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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polymorphism, Single Nucleotide / Diabetes Mellitus, Type 2 / Mendelian Randomization Analysis / Sodium-Glucose Transporter 2 Inhibitors Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: En Journal: Hepatology Year: 2024 Type: Article Affiliation country: South Korea
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polymorphism, Single Nucleotide / Diabetes Mellitus, Type 2 / Mendelian Randomization Analysis / Sodium-Glucose Transporter 2 Inhibitors Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: En Journal: Hepatology Year: 2024 Type: Article Affiliation country: South Korea