Effects of Elobixibat, an Inhibitor of Ileal Bile Acid Transporter, on Glucose and Lipid Metabolism: A Single-arm Pilot Study in Patients with T2DM.

ABSTRACT

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) A1c 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 HbA1c 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 HbA1c, LDL-C, and AA were significantly reduced after administration of elobixibat for 12 weeks (-0.2%, -21.4 mg/dL, and -16.1 µg/dL, respectively; P = 0.016, P < 0.001, and P = 0.010). Period 2 at week 24, the change from baseline in HbA1c 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).