Novel glucose-lowering drugs for non-alcoholic fatty liver disease
The effectiveness of novel glucose-lowering drugs in the management of non-alcoholic fatty liver disease (NAFLD) is not clear. The author Zuo-Di Fu and colleagues published a research paper under the title “Novel glucose-lowering drugs for non-alcoholic fatty liver disease” in the World Journal of Diabetes. The summary of this study is below:
Objective:
To investigate the efficacy of glucose-lowering drugs, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in treating NAFLD.
To conduct a comparison between these treatments.
Method:
The search was conducted systematically for electronic databases. The Randomized controlled trials that compared DPP-4 inhibitors, SGLT2 inhibitors, or GLP-1 RAs against placebo or other active glucose-lowering drugs in NAFLD patients, and acquired outcomes of changes in liver enzyme [aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)] from baseline were included.
Findings:
Investigators conclude novel agents (DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors) help in improving serum ALT and AST levels, improving liver injury, and reducing liver fat in NAFLD patients. Observable reduction in visceral fat area (VFA) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) was also reported. Investigators found that reductions in BMI and body weight, improvement of inflammation and oxidation, improvement in glycemic control, and improvement in insulin resistance might be the possible effect for the treatment of NAFLD with SGLT2 inhibitors and incretin-based therapies.
While GLP-1 RAs and SGLT2 inhibitors possess additive benefits as well, a meta-analysis suggested that GLP-1 RAs can better improve serum ALT levels than SGLT2 inhibitors. Due to a lack of head-to-head studies, it is difficult to conclude which is the most effective treatment. Hence, individualized treatment options could be more effective for patients with different characteristics.
Limitation:
There are chances of biased results as meta-analysis included studies with different baseline characteristics, treatment durations, and predefined outcomes. The study might have low statistical power due to limited numbers of participants with available reports of VFA and MRI-PDFF. There might be heterogeneity across studies because of different diagnostic criteria for NAFLD. As compared to the timescale of progression of NAFLD, trials included were relatively short in duration. Although histological outcomes are considered the gold standard for disease evaluation, there were limited trials with histological outcomes.
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