Background and importance Sodium–glucose co-transporter 2 (SGLT2) inhibitors have been reported to benefit liver function in patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD). Although some systematic reviews and meta-analyses have demonstrated the hepatic benefits from SGLT2 inhibitors in T2D patients with NALFD, the overall findings and quality of these systematic reviews have not been evaluated.
Aim and objectives The aim of this study was to critically appraise existing systematic reviews to consolidate evidence associating the use of SGLT2 inhibitors with beneficial hepatic results for T2D patients with NAFLD.
Material and methods This umbrella review searched relevant published systematic reviews of clinical trials from PubMed and Embase between inception and 16 September 2020. The search strategy combined selected keywords (eg, SGLT2 inhibitors and NAFLD) with MeSH or Emtree terms and directed clinical queries for systematic reviews (eg, systematic (sb) in PUBMED). Articles eligible for inclusion were systematic reviews examining the effectiveness of SGLT2 inhibitors for T2D with NAFLD in clinical trials. Two independent investigators appraised study quality using AMSTAR 2, and extracted the hepatic effects from SGLT2 inhibitors (eg, liver enzymes, liver fat, liver histology, liver cirrhosis and liver cancer) in the included systematic reviews.
Results Of 25 screened potential systematic reviews, we ultimately included seven in this study. However, none 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 review indicated that SGLT2 inhibitors could reduce hepatosteatosis, as supported by biopsy proven evidence of improvement from a small clinical trial, but no evidence of improvement of liver fibrosis was found.
Conclusion and relevance There was some association between SGLT2 inhibitor uses and observed benefits to liver function in T2D patients with NAFLD, although the quality of the current systematic reviews remains relatively low. Further evaluation of long term liver outcomes with SGLT2 inhibitors in liver cirrhosis and liver cancer is warranted.
Conflict of interest No conflict of interest
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