Abstract
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.
Highlights
Type 2 diabetes mellitus is an increasing cause of morbidity and mortality across the world and is strongly associated with obesity
Surgeons have developed a variety of bariatric procedures, including gastric banding, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, that are each effective therapies for obesity but have different effectiveness on type 2 diabetes [2]
Similar results were seen in a 24week study of patients with insulin-treated type 1 diabetes (T1DM) [27], in which the miglitol treated group had a small increase in glucagon-like peptide 1 (GLP-1), reduced glucose-dependent insulinotropic polypeptide (GIP), needed slightly less exogenous insulin and had fewer preprandial hypoglycaemic events
Summary
Type 2 diabetes mellitus is an increasing cause of morbidity and mortality across the world and is strongly associated with obesity. A major focus of new therapeutics is the enteroendocrine system, which produces a wide range of peptide hormones including glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK) and peptideYY (PYY). These act as hormonal signals linking food absorption to physiological responses such as insulin secretion and satiety. Bariatric surgery is an even more effective therapy for diabetes, and is believed to act, at least in part, by mobilising endogenous stores of gut hormones such as GLP-1 and PYY by shifting food absorption from the upper to the lower small intestine, where these hormones are found in higher abundance [2]. This review explores recent progress in, and the potential future of, this approach
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