The use of antidiabetic drug is to be expanded in treating non-alcoholic steatohepatitis (NASH) as the Korean Association for the Study of the Liver (KASL) gave a priority recommendation on prescription of pioglitazone.

The prospective prescription strategy is likely to see a significant change as a glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide, becoming a star obesity drug with exceptional weight-loss effect, has emerged as a new key treatment option.

# On Feb. 17, KASL convened an online hearing session to revise the NASH treatment guideline and unveiled the first draft of the revision scheduled to be published on Mar. 5.

The guideline would vastly revise the year 2013 edition of NASH treatment guideline for the first time in nine years.

The association formed a revision committee last year and held eight sessions of meeting focusing on seeking an evidence-based guideline.

The amended version of the guideline would specify the pharmaceutical therapy in detail, when in 2013 the guideline was published with a simple description. Many of the drugs that accumulated evidences through clinical trial and meta-analysis so far were addressed in the new version.

Most of the pharmaceutical therapies recommended by the new guideline were antidiabetic treatments—pioglitazone, metformin and semaglutide.

First, the guideline recommends administering pioglitazone for treating patients with biopsy-confirmed NASH regardless of underlying diabetes, based on four large-scale studies, including the randomized study published in the New England Journal of Medicine (NEJM) in 2015, proving efficacy of the substance. The evidence level is B1.

However, the guideline also noted a condition to the prescription that the prescriber should be aware of the benefit and risk of the drug as the large-scale randomized study warned of safety issues regarding adverse reaction reported during a long-term prescription.

And for the same reason, metformin was also recommended by the latest guideline with the efficacy in NASH treatment confirmed by a randomized controlled trial that found a six years or more long-term prescription of the drug lower mortality, liver transplant and hepatocellular carcinoma expression rate in patients diagnosed with NASH and liver fibrosis.

Moreover, the newest version of the guideline approved of a GLP-1 RA semaglutide as a priority recommendation. A 72-week Phase II trial with NASH patients observed the drug stopped the fibrosis worsening by 40 percent with 0.1mg dose.

Professor Kim Won of Seoul National University School of Medicine specializing in Internal Medicine evaluated, “Semaglutide seems to show efficacy in treating NASH based on its outstanding weight-loss rate.”

However, other drug like Saxenda (liragultide), also known for the notable weight-loss effect, was not included in the guideline.

The association concluded, liraglutide showed efficacy of improving insulin resistance (IR) and lowering the cardiovascular risk factors, but they were limited in treating diabetes and obesity, and medical evidence relevant to NASH is insufficient.

In the revised draft of the guideline, KASL also added a statin prescription strategy considering the high mortality rate by cardiovascular disease in NASH patients.

In fact, in the GREACE study, statin significantly improved the reduction of the expression of cardiovascular disease in NASH patients, who have increasing liver enzyme concentration. And another clinical trial conducted in South Korea also confirmed the same efficacy.

The head of the treatment guideline revision committee, Professor Cho Yong Kyun (Sungkyunkwan University School of Medicine) noted, “We also reviewed SGLT-2 inhibitor lowering body weight and carnitine combination therapy improving the antioxidant activity, but we could not find enough clinical data regarding the treatment of NASH to be included in the guideline.”