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. 2022 Jun 16;6(7):503-511.
doi: 10.1002/jgh3.12780. eCollection 2022 Jul.

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

Taeang Arai  1 , Masanori Atsukawa  1 , Akihito Tsubota  2 , Hirotaka Ono  1 , Tadamichi Kawano  1 , Yuji Yoshida  1 , Tomomi Okubo  1 , Korenobu Hayama  1 , Ai Nakagawa-Iwashita  1 , Norio Itokawa  1 , Chisa Kondo  1 , Mototsugu Nagao  3 , Katsuhiko Iwakiri  1
Affiliations

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

Taeang Arai et al. JGH Open. .

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.

Keywords: GLP‐1 receptor agonists; controlled attenuation parameter; liver fibrosis; non‐alcoholic fatty liver disease; semaglutide.

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Figures

Figure 1
Figure 1
Changes from baseline in (a) body weight, (b) body mass index (BMI), (c) platelets, (d) aspartate aminotransferase (AST), (e) alanine aminotransferase (ALT), and (f) gamma glutamyl transpeptidase (γ‐GTP) in patients treated with oral semaglutide for 24 weeks. Error bars show the interquartile range. *P < 0.05, **P < 0.01 versus baseline.
Figure 2
Figure 2
Changes from baseline in (a) plasma glucose, (b) hemoglobin A1c (HbA1c), (c) homeostasis model assessment‐insulin resistance (HOMA‐IR), and (d) triglyceride in patients treated with oral semaglutide for 24 weeks. Error bars show the interquartile range. *P < 0.05, **P < 0.01 versus baseline.
Figure 3
Figure 3
Correlation between changes in body weight from baseline to 24 weeks after oral semaglutide treatment and those in levels of (a) alanine aminotransferase (ALT) and (b) controlled attenuation parameter (CAP).
Figure 4
Figure 4
Changes from baseline to 24 weeks after oral semaglutide treatment in (a) fibrosis‐4 (FIB‐4) index, (b) ferritin, (c) type IV collagen 7 s, (d) Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein (WFA+‐M2B), and (e) liver stiffness measurement (LSM). Error bars indicate the interquartile ranges. **P < 0.01 versus baseline. *P < 0.05 versus baseline. NS; not significant.
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