PMID- 36117045 OWN - NLM STAT- MEDLINE DCOM- 20221130 LR - 20221226 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 44 IP - 10 DP - 2022 Oct TI - Effects of Elobixibat, an Inhibitor of Ileal Bile Acid Transporter, on Glucose and Lipid Metabolism: A Single-arm Pilot Study in Patients with T2DM. PG - 1418-1426 LID - S0149-2918(22)00291-0 [pii] LID - 10.1016/j.clinthera.2022.08.009 [doi] AB - PURPOSE: The ileal bile acid transporter inhibitor elobixibat was recently approved in Japan for use in the treatment of patients with chronic constipation. Elobixibat has been associated with increased plasma glucagon-like peptide 1 level through Takeda G protein receptor 5, which is a membrane receptor of bile acids. The present study assessed the metabolic effects of elobixibat in patients with type 2 diabetes mellitus (T2DM)-related constipation. METHODS: In this single-arm pilot study, 21 patients with T2DM and constipation were administered elobixibat 10 mg/d for 12 weeks (period 1). The primary end point was the change in hemoglobin (Hb) A(1c) at week 12. Secondary end points included physical parameters; constipation symptoms; and blood parameters, such as low-density lipoprotein cholesterol (LDL-C), arachidonic acid (AA), and fatty acid fractions. Thereafter, the study participants chose whether to continue therapy for an additional 12 weeks (period 2), at which point HbA(1c) and lipid levels were reevaluated. Safety information, including adverse events, discontinuation and interruption of the drug, was collected at each visit during the trial. FINDINGS: Period 1: the levels of HbA(1c), LDL-C, and AA were significantly reduced after administration of elobixibat for 12 weeks (-0.2%, -21.4 mg/dL, and -16.1 microg/dL, respectively; P = 0.016, P < 0.001, and P = 0.010). Period 2: at week 24, the change from baseline in HbA(1c) was significantly greater among those who continued elobixibat treatment than in those who discontinued after 12 weeks (-0.23% vs +0.21%; P = 0.038). No serious or severe adverse events were observed. IMPLICATIONS: Elobixibat may benefit patients with T2DM by improving glucose metabolism and lowering serum LDL-C and AA levels, in addition to ameliorating constipation. This single-arm pilot study was of a small sample size. The findings provide a basis for designing a larger-scale study to confirm the effects of elobixibat on glucose and lipid metabolism. (UMIN Clinical Trials Registry identifier: UMIN000045508; https://www.umin.ac.jp/ctr/index.htm). CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Yoshinobu, Satoko AU - Yoshinobu S AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Hasuzawa, Nao AU - Hasuzawa N AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. Electronic address: hasuzawa@med.kurume-u.ac.jp. FAU - Nagayama, Ayako AU - Nagayama A AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Iwata, Shimpei AU - Iwata S AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Yasuda, Junichi AU - Yasuda J AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Tokubuchi, Rie AU - Tokubuchi R AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Kabashima, Masaharu AU - Kabashima M AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Gobaru, Mizuki AU - Gobaru M AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Hara, Kento AU - Hara K AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Murotani, Kenta AU - Murotani K AD - Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan. FAU - Moriyama, Yoshinori AU - Moriyama Y AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Ashida, Kenji AU - Ashida K AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. FAU - Nomura, Masatoshi AU - Nomura M AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurumes. LA - eng SI - UMIN-CTR/UMIN000045508 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220916 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (bile acid binding proteins) RN - 0 (Cholesterol, LDL) RN - 865UEK4EJC (elobixibat) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glycated Hemoglobin A) SB - IM MH - Humans MH - Cholesterol, LDL MH - Constipation/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucose MH - Glycated Hemoglobin/metabolism MH - Lipid Metabolism MH - Pilot Projects OTO - NOTNLM OT - Bile acid OT - Elobixibat OT - HbA(1c) OT - Ileal bile acid transporter inhibitor OT - LDL-C OT - Type 2 diabetes EDAT- 2022/09/19 06:00 MHDA- 2022/11/23 06:00 CRDT- 2022/09/18 22:06 PHST- 2022/04/13 00:00 [received] PHST- 2022/08/10 00:00 [revised] PHST- 2022/08/18 00:00 [accepted] PHST- 2022/09/19 06:00 [pubmed] PHST- 2022/11/23 06:00 [medline] PHST- 2022/09/18 22:06 [entrez] AID - S0149-2918(22)00291-0 [pii] AID - 10.1016/j.clinthera.2022.08.009 [doi] PST - ppublish SO - Clin Ther. 2022 Oct;44(10):1418-1426. doi: 10.1016/j.clinthera.2022.08.009. Epub 2022 Sep 16.