Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of liver disease, specifically chronic liver disease. Type 2 diabetes (T2DM) is associated with the risk of NAFLD given that patients usually have insulin resistance as one of the observed complications with NAFLD. Hypoglycemic agents, including sodium glucose cotransporter 2 (SGLT-2), have shown to improve NAFLD. The objective of this study is to evaluate the effect of SGLT-2 inhibitors on NAFLD patients’ outcomes, whether they have T2DM or not. We conducted a comprehensive search using the PubMed and Ovid databases to identify published studies that addressed the use of SGLT-2 inhibitors in NAFLD patients. The outcomes assessed include changes in liver enzymes, lipid profiles, weight changes, the fibrosis-4-index (FIB4), and magnetic resonance imaging proton density-based fat fraction (MRI-PDFF). Only clinical trials that met the quality measures were included in this review. Out of 382 potential studies, we included 16 clinical trials that discussed the use of SGLT-2 inhibitors in NAFLD patients. A total of 753 patients were enrolled in these trials. The majority of the trials reported positive effects of SGLT-2 inhibitors on liver enzymes; alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase. All 10 trials that reported changes in body mass index (BMI) from baseline showed a statistically significant reduction with SGLT-2 inhibitor use, while 11 studies reported a significant increase in high density lipoprotein (HDL) levels, 3 studies reported a reduction in triglycerides (TG) levels, and 2 studies showed a decrease in low density lipoprotein (LDL) levels. The available evidence shows that the use of SGLT-2 inhibitors in NAFLD is associated with positive outcomes on liver enzymes, lipid profiles, and BMI. Further studies with larger sample size and longer follow-up time are warranted.
[http://dx.doi.org/10.1038/nrgastro.2017.109] [PMID: 28930295]
[http://dx.doi.org/10.1016/j.jhep.2014.12.012] [PMID: 25920090]
[http://dx.doi.org/10.1002/hep.29367] [PMID: 28714183]
[http://dx.doi.org/10.1016/j.jhep.2017.10.031] [PMID: 29128391]
[http://dx.doi.org/10.1016/S2213-8587(14)70032-4] [PMID: 24731669]
[http://dx.doi.org/10.3390/ijms21165888] [PMID: 32824337]
[http://dx.doi.org/10.1038/550S101a]
[http://dx.doi.org/10.1016/j.jhep.2020.03.039] [PMID: 32278004]
[http://dx.doi.org/10.1038/nature10809] [PMID: 22297845]
[http://dx.doi.org/10.1111/liv.14669] [PMID: 32946642]
[http://dx.doi.org/10.1093/ehjopen/oeac030] [PMID: 35919342]
[http://dx.doi.org/10.1002/hep.21178] [PMID: 16729309]
[http://dx.doi.org/10.1007/s10620-016-4079-4] [PMID: 27017224]
[http://dx.doi.org/10.1007/s00330-019-06072-4] [PMID: 30899974]
[http://dx.doi.org/10.1016/S0016-5085(99)70506-8] [PMID: 10348825]
[http://dx.doi.org/10.1002/hep.20701] [PMID: 15915461]
[http://dx.doi.org/10.1038/nrgastro.2016.147] [PMID: 27729660]
[http://dx.doi.org/10.1016/j.jhep.2019.06.021] [PMID: 31279902]
[http://dx.doi.org/10.1111/dom.12973] [PMID: 28417532]
[http://dx.doi.org/10.1007/s11892-021-01383-7] [PMID: 33742318]
[http://dx.doi.org/10.1016/j.eprac.2022.03.010] [PMID: 35569886]
[http://dx.doi.org/10.1136/bmj.d5928] [PMID: 22008217]
[http://dx.doi.org/10.1186/2046-4053-4-1/TABLES/4]
[http://dx.doi.org/10.2337/dc19-0641] [PMID: 31540903]
[http://dx.doi.org/10.1111/jdi.13279] [PMID: 32329963]
[http://dx.doi.org/10.3390/jcm9010259] [PMID: 31963648]
[http://dx.doi.org/10.1002/jgh3.12274] [PMID: 31609493]
[http://dx.doi.org/10.2337/dc17-0518] [PMID: 28751548]
[http://dx.doi.org/10.2337/dc18-0165] [PMID: 29895557]
[http://dx.doi.org/10.1111/dom.13520] [PMID: 30178600]
[http://dx.doi.org/10.1111/dom.13061] [PMID: 28719078]
[http://dx.doi.org/10.2147/DMSO.S184767] [PMID: 30568471]
[http://dx.doi.org/10.1007/s13340-016-0302-y]
[http://dx.doi.org/10.1111/ijcp.13335] [PMID: 30810254]
[http://dx.doi.org/10.1111/hepr.13304] [PMID: 30577089]
[http://dx.doi.org/10.1016/j.curtheres.2017.07.002] [PMID: 28912902]
[http://dx.doi.org/10.1007/s00125-018-4675-2] [PMID: 29971527]
[http://dx.doi.org/10.1002/osp4.294] [PMID: 30338118]
[http://dx.doi.org/10.1111/jdi.12980] [PMID: 30461221]
[http://dx.doi.org/10.1002/oby.22066] [PMID: 29165885]
[http://dx.doi.org/10.1002/oby.23331] [PMID: 34932882]
[http://dx.doi.org/10.3390/ijms23063107] [PMID: 35328527]
[http://dx.doi.org/10.3389/fendo.2021.635556] [PMID: 34220701]
[http://dx.doi.org/10.1111/jgh.15202] [PMID: 33439540]
[http://dx.doi.org/10.4239/wjd.v12.i1.84] [PMID: 33520110]
[http://dx.doi.org/10.1111/hepr.13645] [PMID: 33847462]
[http://dx.doi.org/10.1503/cmaj.1040752] [PMID: 15684121]
[http://dx.doi.org/10.1161/01.ATV.0000122852.22604.78] [PMID: 14976002]
[http://dx.doi.org/10.1381/096089206778663805] [PMID: 17059735]
[http://dx.doi.org/10.1111/jgh.14577] [PMID: 30551263]
[http://dx.doi.org/10.1136/gutjnl-2015-309265] [PMID: 25873639]
[http://dx.doi.org/10.1148/radiol.2017170550] [PMID: 28892458]
[http://dx.doi.org/10.1002/jmri.25006] [PMID: 26201284]
[http://dx.doi.org/10.1002/jmri.21147] [PMID: 17969166]