Article Text

SGLT2 inhibitors in patients with type 2 diabetes with non-alcoholic fatty liver diseases: an umbrella review of systematic reviews
  1. Shih-Chieh Shao1,2,
  2. Liang-Tseng Kuo3,4,
  3. Rong-Nan Chien4,5,6,
  4. Ming-Jui Hung4,7,
  5. Edward Chia-Cheng Lai2,8
  1. 1Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
  2. 2School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  3. 3Division of Sports Medicine, Department of Orthopaedic Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
  4. 4College of Medicine, Chang Gung University, Taoyuan, Taiwan
  5. 5Liver Research Unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
  6. 6Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
  7. 7Section of Cardiology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
  8. 8Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan
  1. Correspondence to Dr Edward Chia-Cheng Lai; edward_lai{at}


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

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  • 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.

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