Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions

Abstract

Provided herein are methods of utilizing bile acid transport inhibitors and/or enteroendocrine peptide enhancing agents for the treatment of obesity, diabetes, and inflammatory gastrointestinal conditions.

1 .- 26 . (canceled) 
     
     
         27 . A method of reducing side effects associated with an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) treatment in an individual in need thereof by non-systemically administering a therapeutically effective amount of the ASBTI to the distal ileum, the colon, or the rectum of the individual, wherein the ASBTI is selected from 
       
         
           
           
               
               
           
         
       
       and potassium((2R,3R,4S,5R,6R)-4-benzyloxy-6-{3-[3-((3S,4R,5R)-3-butyl-7-dimethylamino-3-ethyl-4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]thiepin-5-yl)-phenyl]-ureido}-3,5-dihydroxy-tetrahydropyran-2-ylmethyl)sulphate ethanolate hydrate. 
     
     
         28 . The method of  claim 27 , further comprising administering a second agent selected from an enteroendocrine peptide enhancing agent, a nuclear farnesoid X receptor (FXR) agonist, a liver receptor homolog 1 (LRH-1), a DPP-IV inhibitor, a proton pump inhibitor, H2 antagonist, prokinetic agent, a biguanide, an incretin mimetic, a thiazolidinone, a mucoadhesive agent, and GLP-1 or an analog thereof. 
     
     
         29 . The method of  claim 27 , wherein the individual is a prematurely born infant, an enterally-fed infant, or a formula-fed infant. 
     
     
         30 . The method of  claim 27 , wherein the ASBTI increases the concentration of bile acids and salts thereof in the distal gastrointestinal tract of an individual. 
     
     
         31 . The method of  claim 27 , wherein the ASBTI is 
       
         
           
           
               
               
           
         
       
     
     
         32 . The method of  claim 27 , wherein the ASBTI is potassium((2R,3R,4S,5R,6R)-4-benzyloxy-6-{3-[3-((3S,4R,5R)-3-butyl-7-dimethylamino-3-ethyl-4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]thiepin-5-yl)-phenyl]-ureido}-3,5-dihydroxy-tetrahydropyran-2-ylmethyl)sulphate ethanolate hydrate, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         33 . The method of  claim 27 , wherein the ASBTI is administered before ingestion of food. 
     
     
         34 . The method of  claim 27 , wherein the ASBTI is administered less than about 60 minutes before ingestion of food. 
     
     
         35 . The method of  claim 27 , wherein the ASBTI is administered less than about 30 minutes before ingestion of food. 
     
     
         36 . The method of  claim 27 , wherein the ASBTI is administered orally. 
     
     
         37 . The method of  claim 27 , wherein less than 10% of the ASBTI is systemically absorbed. 
     
     
         38 . The method of  claim 27 , wherein less than 30% of the ASBTI is systemically absorbed.