Effect of sodium-glucose cotransporter 2 inhibitor in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a propensity score-matched analysis of real-world data

Taeang Arai; Masanori Atsukawa; Akihito Tsubota; Shigeru Mikami; Hiroki Ono; Tadamichi Kawano; Yuji Yoshida; Tomohide Tanabe; Tomomi Okubo; Korenobu Hayama; Ai Nakagawa-Iwashita; Norio Itokawa; Chisa Kondo; Keiko Kaneko; Naoya Emoto; Mototsugu Nagao; Kyoko Inagaki; Izumi Fukuda; Hitoshi Sugihara; Katsuhiko Iwakiri

doi:10.1177/20420188211000243

Effect of sodium-glucose cotransporter 2 inhibitor in patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus: a propensity score-matched analysis of real-world data

Ther Adv Endocrinol Metab. 2021 Mar 21:12:20420188211000243. doi: 10.1177/20420188211000243. eCollection 2021.

Authors

Taeang Arai¹, Masanori Atsukawa², Akihito Tsubota³, Shigeru Mikami⁴, Hiroki Ono¹, Tadamichi Kawano¹, Yuji Yoshida⁵, Tomohide Tanabe¹, Tomomi Okubo⁵, Korenobu Hayama⁵, Ai Nakagawa-Iwashita¹, Norio Itokawa¹, Chisa Kondo¹, Keiko Kaneko¹, Naoya Emoto⁶, Mototsugu Nagao⁷, Kyoko Inagaki⁷, Izumi Fukuda⁷, Hitoshi Sugihara⁷, Katsuhiko Iwakiri¹

Affiliations

¹ Division of Gastroenterology and Hepatology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
² Division of Gastroenterology and Hepatology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
³ Core Research Facilities for Basic Science, Research Center for Medical Sciences, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
⁴ Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Miyazaki Noda, Japan.
⁵ Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Inzai-shi, Chiba, Japan.
⁶ Division of Endocrinology, Nippon Medical School Chiba Hokusoh Hospital, Inzai-shi, Chiba, Japan.
⁷ Division of Endocrinology, Diabetes and Metabolism, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.

Abstract

Background: Although sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve not only glycemic control but also liver inflammation and fatty changes in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), its sustainability and effect on liver fibrosis have remained unclear. The current study aimed to clarify the effects of 48-week SGLT2-I therapy on liver inflammation, fatty changes, and fibrosis in NAFLD patients with T2DM.

Methods: This study evaluated the effects of SGLT2-I on NAFLD, including liver fibrosis assessed via transient elastography, in 56 patients with NAFLD who received SGLT2-I for 48 weeks. Moreover, changes in each clinical parameter between patients receiving SGLT2-I (the SGLT2-I group) and those receiving other oral hypoglycemic agents (OHAs) (the non-SGLT2-I group) were compared, using 1:1 propensity score matching to adjust for baseline factors.

Results: The SGLT2-I group exhibited a significant decrease in controlled attenuation parameter (312 dB/m at baseline to 280 dB/m at week 48) and liver stiffness measurement (9.1-6.7 kPa) (p < 0.001 for both). After propensity score matching (44 patients each in the SGLT2-I and non-SGLT2-I groups), no significant difference in HbA1c decrease was observed between the two groups. However, compared with the non-SGLT2-I group, the SGLT2-I group showed a significant decrease in body weight (p < 0.001), alanine aminotransferase (p = 0.02), uric acid (p < 0.001), and Fibrosis-4 (FIB-4) index (p = 0.01) at week 48. The improvement in FIB-4 index, defined as a ⩾10% decline from baseline at week 48, was 56.8% (25/44) in the SGLT2-I group and 20.5% (9/44) in the non-SGLT2-I group (p < 0.001).

Conclusion: SGLT2-Is improved not only glycemic control but also liver fatty infiltration and fibrosis in patients with NAFLD and T2DM, suggesting their possible superiority to other OHAs concerning these effects.

Keywords: non-alcoholic fatty liver disease; sodium-glucose cotransporter 2 inhibitor; transient elastography; type 2 diabetes mellitus.