Efficacy and safety of oral semaglutide in patients with non‐alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study

Abstract

Background and Aim: This study aimed to clarify the efficacy and safety of oral semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Methods: This was a single-arm, open-label pilot study. Sixteen patients with NAFLD who received oral semaglutide for T2DM were included in the analysis. Oral semaglutide was initiated at a dose of 3 mg once daily, and the dose was sequentially increased to 7 mg at 4 weeks and 14 mg at 8 weeks (maintenance dose) until the end of the 24-week trial. Results: Body weight and levels of liver-related biochemistry, plasma glucose, and hemoglobin A1c decreased significantly from baseline to 12 weeks. These significant decreases were maintained until the end of the trial. Additionally, levels of the homeostasis model assessment-insulin resistance and triglyceride significantly decreased at 24 weeks. Controlled attenuation parameter (CAP) values significantly decreased from baseline to 24 weeks. Changes in body weight were correlated with those in levels of alanine aminotransferase (r = 0.52) and CAP (r = 0.72). As for liver fibrosis markers, significant decreases from baseline to 24 weeks in levels of the fibrosis-4 index, ferritin, and type IV collagen 7 s were found; however, the liver stiffness measurement did not significantly decrease. Most adverse events were grade 1-2 transient gastrointestinal disorders. Conclusions: Oral semaglutide treatment in patients with NAFLD complicated by T2DM improved impaired liver function, hypertriglyceridemia, insulin resistance, and hepatic steatosis, as well as improving diabetic status and reducing body weight.

Once-Weekly Subcutaneous Semaglutide Improves Fatty Liver Disease in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study

“…Similarly, satisfactory effects on liver steatosis but not liver stiffness were confirmed in a study using magnetic resonance imaging to assess changes in liver parenchyma [ 44 ]. Finally, a very recent pilot study tested the oral formulation of Semaglutide for 24 weeks in 16 TD2 patients with NAFLD, showing results consistent with our findings [ 45 ].…”

A Significant Effect of Oral Semaglutide on Cardiovascular Risk Factors in Patients With Type 2 Diabetes

“…Furthermore, since an elevation of VLDL is commonly observed in an insulin resistant-state [ 9 , 10 ], a decrease of VLDL suggests an improvement of diabetic dyslipidemia due to insulin resistance. Arai et al studied the efficacy and safety of oral semaglutide in 16 type 2 diabetic patients with non-alcoholic fatty liver disease [ 11 ]. In their study, body weight, liver function and HbA1c were significantly improved after 12 weeks.…”

Why do some glucose‐lowering agents improve non‐alcoholic fatty liver disease whereas others do not? A narrative review in search of a unifying hypothesis

“…58,[61][62][63][64][65] A trial has been designed to evaluate oral semaglutide in hepatic steatosis (NCT03884075) and a pilot study has shown that this new drug formulation improves indexes of hepatic steatosis and fibrosis in T2D subjects. 66 It has been shown that GLP-1 RA enhances insulin sensitivity in the liver and WAT and reduces DNL and WAT lipolysis, possibly with a direct effect on the lipolysis pathway, consequently reducing FFA flux to other tissues, [67][68][69] as shown in Table 1. These drugs improve IR in WAT and increase adiponectin levels, improving adipose tissue function and redistributing lipids.…”

“…Exenatide, liraglutide and dulaglutide reduce hepatic fat content assessed by magnetic resonance; liraglutide and semaglutide reduce the histological features of NASH, thus preventing the worsening of inflammation but have no effect on liver fibrosis stages or in NASH‐related cirrhosis 58,61–65 . A trial has been designed to evaluate oral semaglutide in hepatic steatosis (NCT03884075) and a pilot study has shown that this new drug formulation improves indexes of hepatic steatosis and fibrosis in T2D subjects 66 …”