| Title: | Inhibition of sodium-glucose cotransporter-2 and liver-related complications in individuals with diabetes: a Mendelian randomization and population-based cohort study. |
| Journal: | Hepatology |
| Published: | 11 Mar 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38466796/ |
| DOI: | https://doi.org/10.1097/hep.0000000000000837 |
Publication 10140
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
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.</p>
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.</p>
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.</p>
17 Authors
- Sung Won Chung
- Hye-Sung Moon
- Hyunjae Shin
- Hyein Han
- Sehoon Park
- Heejin Cho
- Jeayeon Park
- Moon Haeng Hur
- Min Kyung Park
- Sung-Ho Won
- Yun Bin Lee
- Eun Ju Cho
- Su Jong Yu
- Dong Ki Kim
- Jung-Hwan Yoon
- Jeong-Hoon Lee
- Yoon Jun Kim
1 Application
| Application ID | Title |
|---|---|
| 53799 | Impact of genetic and environmental factors on the health-related outcomes in chronic kidney disease patients |
Enabling scientific discoveries that improve human health