Pioglitazone, Vitamin E, SGLT2 inhibitors, and GLP-1 receptor agonists are effective for treatment of NAFLD patients.

A study was carried out to determine efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists, vitamin E, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and pioglitazone in people suffering from non-alcoholic fatty liver disease (NAFLD).

Databases like Cochrane Library, PubMed, Web of Science, and Embase were comprehensively explored to find out randomized controlled trials that compared the impact of four different drugs in NAFLD.  In this systematic review and network meta-analysis, the drugs investigated were pioglitazone, vitamin E (δ-tocotrienol, α-tocopherol), three kinds of GLP-1 receptor agonists (dulaglutide, liraglutide, semaglutide), and four SGLT2 inhibitors (empagliflozin, dapagliflozin, tofogliflozin, ipragliflozin). As a reference, placebos were utilized.

The endpoints incorporated alteration in invasive tests [resolution of non-alcoholic steatohepatitis (NASH), fibrosis score] and non-invasive tests [keratin-18, alanine aminotransferase (ALT), enhanced liver fibrosis (ELF) score, gamma-glutamyl transferase (GGT), controlled attenuation parameter (CAP), liver fat content, aspartate aminotransferase (AST)]. In total, 27 trials and 3,416 volunteers were included.

δ-Tocotrienol showed superiority over placebo in reducing the GGT level. When compared to placebo, pioglitazone, semaglutide, and ipragliflozin elicited a considerably greater drop in the ALT level. Dapagliflozin, semaglutide, and pioglitazone displayed superiority over placebo in lowering the level of AST. Pioglitazone and tofogliflozin (vs. placebo) elicited a remarkably greater drop in keratin-18 levels. In terms of CAP reduction, liraglutide was better than placebo.

Compared to placebo, vitamin E, liraglutide, and pioglitazone elicited a considerably greater rise in NASH resolution. Regarding pairwise comparisons, pioglitazone and semaglutide showed superiority over liraglutide in minimizing the level of ALT. Semaglutide (vs. dulaglutide) triggered a greater reduction in ALT levels. In terms of reduction of AST level, semaglutide was witnessed to be better than tofogliflozin, empagliflozin, dulaglutide, and liraglutide.

Pioglitazone stimulated a better reduction in GGT level when compared to ipragliflozin. δ-Tocotrienol was noted to be superior to liraglutide in minimizing the level of GGT. Pioglitazone and tofogliflozin instigated more reduction in keratin-18 levels in comparison with dulaglutide. Regarding an increase in NASH resolution, pioglitazone was found to be superior to vitamin E.

Moreover, liraglutide therapy exhibited the highest surface under the cumulative ranking
(SUCRA) in minimizing CAP and ELF scores and improving NASH resolution while pioglitazone therapy illustrated the highest SUCRA ranking in lowering fibrosis scores and liver fat content. Tofogliflozin use showed the highest SUCRA ranking in diminishing keratin-18, while dapagliflozin use demonstrated the highest SUCRA ranking in lowering GGT level. In terms of reduction of levels of AST and ALT, semaglutide therapy possessed the highest SUCRA ranking

Hence, this study offered evidence for the effectiveness of pioglitazone, vitamin E, GLP-1 receptor agonists, and SGLT2 inhibitors for management of people having NAFLD.