Targeted intestinal delivery of incretin secretagogues - towards new diabetes and obesity therapies

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Gribble, FM 
Meek, CL 

A new strategy under development for the treatment of type 2 diabetes and obesity is to mimic some of the effects of bariatric surgery by delivering food-related stimuli to the distal gastrointestinal tract where they should enhance the release of gut hormones such as glucagon-like peptide-1 (GLP-1) and peptideYY (PYY). Methods include inhibition of food digestion and absorption in the upper GI tract, or oral delivery of stimuli in capsules or pelleted form to protect them against gastric degradation. A variety of agents have been tested in humans using capsules, microcapsules or pellets, delivering nutrients, bile acids, fatty acids and bitter compounds. This review examines the outcomes of these different approaches and supporting evidence from intestinal perfusion studies.

Enteroendocrine hormones, peptideYY (PYY), Glucagon-like peptide-1 (GLP-1), Diabetes, Obesity, Capsules, Pellets, Infusion
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Medical Research Council (MC_UU_12012/3)
Wellcome Trust (106262/Z/14/Z)
MRC (MC_UU_00014/5)
FMG and FR are funded by grants from the Medical Research Council (MRC_MC_UU_12012/3) and Wellcome Trust (grants 106262/Z/14/Z and 106263/Z/14/Z). The study of MOG and STC capsules was supported by Full4Health (FP7/2011-2015, grant agreement no. 266408), and plasma GLP-1 analysis was performed by the Addenbrooke’s Core Biochemical Assay Laboratory. CLM was funded by the Wellcome Trust/Glaxo SmithKline TMAT Programme.