PMID- 35312970 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1869-6953 (Print) IS - 1869-6961 (Electronic) IS - 1869-6961 (Linking) VI - 13 IP - 5 DP - 2022 May TI - Additional Effect of Luseogliflozin on Semaglutide in Nonalcoholic Steatohepatitis Complicated by Type 2 Diabetes Mellitus: An Open-Label, Randomized, Parallel-Group Study. PG - 1083-1096 LID - 10.1007/s13300-022-01239-7 [doi] AB - INTRODUCTION: Untreated nonalcoholic fatty liver may progress to nonalcoholic steatohepatitis (NASH) and cirrhosis and induce hepatocellular carcinoma and liver failure. Type 2 diabetes mellitus (T2DM), often complicated with nonalcoholic fatty liver disease (NAFLD), is a driver of NAFLD progression. Thus, efficacious treatment strategies for patients with coexisting NAFLD and T2DM are important for preventing NAFLD progression. Although previous studies have demonstrated that either sodium-glucose transporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1 RAs) benefit NASH patients with T2DM, the rate of NASH resolution has not sufficiently improved. Therefore, we developed a protocol for a randomized controlled trial to examine whether the addition of an SGLT2i to the treatment regimen of patients receving a GLP-1 RA (combination therapy), within the therapeutic dose range for T2DM, increases the rate of NASH resolution in patients with coexisting NASH and T2DM. METHODS: This open-label, randomized, parallel-group study commenced in June 2021, will conclude recruitment in May 2023, and will end by March 2025. Sixty patients with NASH complicated by T2DM are enrolled at the Ehime University Hospital in Toon, Japan. Participants will be randomized into: (1) an intervention group receiving combination therapy with the SGLT2i luseogliflozin 2.5 mg, once daily (Taisho Pharmaceutical, Tokyo, Japan) and the GLP-1 RA semaglutide 0.5 mg, once per week (Novonordisk, Copenhagen, Denmark); and (2) a control group receiving monotherapy with the GLP-1 analog semaglutide. The primary endpoints, which will be ascertained by liver biopsy, are: (1) NASH resolution rate from baseline without worsening of liver fibrosis after 52 weeks of intervention; (2) rate of improvement from baseline of at least 1 point in the NAFLD activity score without worsening of liver fibrosis after 52 weeks of intervention; and (3) rate of improvement from baseline of at least one fibrosis stage without worsening of NASH after 52 weeks of intervention. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) number: UMIN000045003. Japan Registry of Clinical Trials registration number: jRCTs061210009. CI - (c) 2022. The Author(s). FAU - Miyake, Teruki AU - Miyake T AUID- ORCID: 0000-0002-9905-5356 AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. miyake.teruki.mg@ehime-u.ac.jp. FAU - Yoshida, Osamu AU - Yoshida O AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Matsuura, Bunzo AU - Matsuura B AD - Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan. FAU - Furukawa, Shinya AU - Furukawa S AD - Health Service Center, Ehime University, Bunkyo, Matsuyama, Ehime, Japan. FAU - Hirooka, Masashi AU - Hirooka M AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Abe, Masanori AU - Abe M AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Tokumoto, Yoshio AU - Tokumoto Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Koizumi, Yohei AU - Koizumi Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Watanabe, Takao AU - Watanabe T AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Takeshita, Eiji AU - Takeshita E AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Sunago, Kotaro AU - Sunago K AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Yukimoto, Atsushi AU - Yukimoto A AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Watanabe, Kyoko AU - Watanabe K AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Miyazaki, Masumi AU - Miyazaki M AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Kanzaki, Sayaka AU - Kanzaki S AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Nakaguchi, Hironobu AU - Nakaguchi H AD - Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan. FAU - Koizumu, Mitsuhito AU - Koizumu M AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Yamamoto, Yasunori AU - Yamamoto Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. FAU - Kumagi, Teru AU - Kumagi T AD - Post-Graduate Medical Education Center, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan. FAU - Hiasa, Yoichi AU - Hiasa Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan. LA - eng PT - Journal Article DEP - 20220321 PL - United States TA - Diabetes Ther JT - Diabetes therapy : research, treatment and education of diabetes and related disorders JID - 101539025 PMC - PMC9076799 OTO - NOTNLM OT - Luseogliflozin OT - Nonalcoholic steatohepatitis OT - Semaglutide OT - Type 2 diabetes mellitus EDAT- 2022/03/22 06:00 MHDA- 2022/03/22 06:01 PMCR- 2022/03/21 CRDT- 2022/03/21 17:19 PHST- 2022/01/16 00:00 [received] PHST- 2022/02/23 00:00 [accepted] PHST- 2022/03/22 06:00 [pubmed] PHST- 2022/03/22 06:01 [medline] PHST- 2022/03/21 17:19 [entrez] PHST- 2022/03/21 00:00 [pmc-release] AID - 10.1007/s13300-022-01239-7 [pii] AID - 1239 [pii] AID - 10.1007/s13300-022-01239-7 [doi] PST - ppublish SO - Diabetes Ther. 2022 May;13(5):1083-1096. doi: 10.1007/s13300-022-01239-7. Epub 2022 Mar 21.