A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease

Abstract

Objective:

To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH).

Data Sources:

MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors.

Study Selection and Data Extraction:

Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated.

Data Synthesis:

Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH.

Relevance to Patient Care and Clinical Practice:

Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS.

Conclusions:

Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.