Introduction Sodium glucose co-transporter 2 (SGLT2) inhibitors have been reported to benefit liver functions in patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD). The aim of this study is to critically appraise existing systematic reviews in order to consolidate evidence associating the use of SGLT2 inhibitors with beneficial hepatic results for patients with T2D with NAFLD.
Methods This umbrella review searched relevant published systematic reviews of clinical trials from PubMed and Embase between inception and September 16, 2020. Two independent investigators appraised study quality using AMSTAR2 (Assessment of Multiple Systematic Reviews 2). The hepatic effects from SGLT2 inhibitors were summarized based on liver enzymes, liver fat, liver histology, liver cirrhosis and liver cancer.
Results Of 25 screened potential systematic reviews, we ultimately included 7 in this study. However, none of them could be rated as being of high methodological quality. Five systematic reviews indicated that SGLT2 inhibitors could effectively decrease liver fat and liver parameters of alanine aminotransferase and gamma-glutamyl transferase in patients with NAFLD. Two systematic reviews indicated that SGLT2 inhibitors could reduce hepatosteatosis, as supported by biopsy-proven evidence of improvement from a small clinical trial, but no evidence of liver fibrosis improvement was found.
Conclusions There is some association between SGLT2 inhibitor use and observed benefits to liver functions in patients with T2D with NAFLD, although the quality of current systematic reviews remains relatively low. Further evaluation of long-term liver outcomes with SGLT2 inhibitors in cases of liver cirrhosis and liver cancer is warranted.
- diabetes mellitus
- type 2
- drug therapy
- fatty liver
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Contributors The proposal for this study was developed by S-CS and EC-CL and reviewed by all authors. The content of this manuscript was agreed upon by all authors. The descriptive analysis was conducted by S-CS and L-TK. The first draft of the manuscript was developed by S-CS and critically reviewed by all authors. All authors approved the final version of the manuscript before its submission. S-CS is the guarantor of this work.
Funding This study received a grant from Chang Gung Medical Foundation (CMRPG3H1552) and the Ministry of Science and Technology of Taiwan (107-2320-B-006-070-MY3), which had no role in study design, analysis, interpretation or reporting of results.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.