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. 2021 May 31;36(3):e273.
doi: 10.5001/omj.2021.62. eCollection 2021 May.

Effect of SGLT-2 Inhibitors on Non-alcoholic Fatty Liver Disease among Patients with Type 2 Diabetes Mellitus: Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials

Kai Wei Lee  1 , Navin Kumar Devaraj  1   2 , Siew Mooi Ching  1   2 , Sajesh K Veettil  3 , Fan Kee Hoo  4 , Inas Deuraseh  1 , Man Jun Soo  1
Affiliations

Effect of SGLT-2 Inhibitors on Non-alcoholic Fatty Liver Disease among Patients with Type 2 Diabetes Mellitus: Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials

Kai Wei Lee et al. Oman Med J. .

Abstract

Objectives: Non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) is a common problem associated with obesity and type 2 diabetes mellitus (T2DM). There have been anecdotal reports of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) in improving liver function parameters in those with concomitant T2DM and NAFLD/NASH. We sought to systematically evaluate the evidence of SGLT2Is in improving liver function parameters in T2DM patients with NAFLD, considering the risks of random error based on trial sequential analysis (TSA). We also performed a meta-analysis based on a random-effects model.

Methods: A systematic literature search was performed using the Medline, Cochrane, and Embase databases from inception to 20 October 2018. Primary outcome for meta-analyses was the changes in hepatic enzyme levels (alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase). We also performed a meta-analysis on changes in insulin resistance, glycemic, and lipid parameters using SGLT2Is as a secondary objective.

Results: Eight eligible randomized controlled studies were eligible for analysis. Meta-analysis showed the efficacy of two SLT2Is, dapagliflozin, and canagliflozin in reducing these enzymes level. TSA showed that canagliflozin significantly reduced the gamma-glutamyl transpeptidase level by weighted mean difference (-5.474, 95% confidence interval (CI): -6.289??-4.659) compared to others comparators, and the evidence is conclusive. Dapagliflozin also had a statistically significant reduction in glycated hemoglobin, which is a parameter of glycemic control and homeostatic model assessment for insulin sensitivity (HOMA-IR), which is a parameter of insulin sensitivity by a weight mean difference, -0.732 (95% CI: -1.087??-0.378) and -0.804 (95% CI: -1.336??0.272), respectively.

Conclusions: This study indicated that canagliflozin effectively improves liver function parameters among patients with diabetes, while dapagliflozin is more effective in improving glycemic indices and insulin sensitivity.

Keywords: Canagliflozin; Non-alcoholic Fatty Liver Disease; Sodium-Glucose Transporter 2 Inhibitors.

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Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the literature screening process.
Figure 2
Figure 2
Meta-analysis on the effect of dapagliflozin versus comparators on alanine transaminase (ALT) reduction.
Figure 3
Figure 3
Meta-analysis on the effect of canagliflozin versus comparators on alanine transaminase (ALT) reduction.
Figure 4
Figure 4
Meta-analysis on the effect of dapagliflozin versus comparators on aspartate transaminase (AST) reduction.
Figure 5
Figure 5
Meta-analysis on the effect of canagliflozin versus comparators on aspartate transaminase (AST) reduction.
Figure 6
Figure 6
Meta-analysis on the effect of dapagliflozin versus comparators on gamma-glutamyl transpeptidase (GGT) reduction.
Figure 7
Figure 7
Meta-analysis on the effect of canagliflozin versus comparators on gamma-glutamyl transpeptidase (GGT) reduction.
Appendix
Appendix
3a: Trial sequential analysis on the effect of dapagliflozin vs. comparators on ALT reduction.
Appendix
Appendix
3b: Trial sequential analysis on the effect of canagliflozin versus comparators on ALT reduction.
Appendix
Appendix
3c: Trial sequential analysis on the effect of dapagliflozin versus comparators on AST reduction.
Appendix
Appendix
3d: Trial sequential analysis on the effect of canagliflozin versus comparators on AST reduction.
Appendix
Appendix
3e: Trial sequential analysis on the effect of dapagliflozin versus comparators on GGT reduction.
Appendix
Appendix
3f: Trial sequential analysis on the effect of canagliflozin versus comparators on GGT reduction.
Appendix 4
Appendix 4
Risk of bias graph: review authors?? judgments about each risk of bias item presented as percentages across all included studies.
Appendix 5
Appendix 5
Risk of bias summary: review authors?? judgments about each risk of bias item for each included study.
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