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Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer

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AIMS: Sevelamer, a non-absorbable amine-based resin used for treatment of hyperphosphatemia, has been demonstrated to hold a marked bile acid-binding potential alongside beneficial effects on lipid and glucose metabolism. The aim of this study was to investigate the glucose-lowering effect and mechanism(s) of sevelamer in patients with type 2 diabetes.

MATERIALS AND METHODS: In this double-blinded randomized controlled trial, we randomized 30 patients with type 2 diabetes to sevelamer (n=20) or placebo (n=10). Participants were subjected to standardized 4-hour liquid meal tests at baseline and following seven days of treatment. The main outcome measure was plasma glucagon-like peptide-1 excursions as measured by area under the curve. In addition, blood was sampled for measurements of glucose, lipids, glucose-dependent insulinotropic polypeptide, C-peptide, glucagon, fibroblast growth factor-19, cholecystokinin and bile acids. Assessments of gastric emptying, resting energy expenditure and gut microbiota composition were performed.

RESULTS: Sevelamer elicited a significant placebo-corrected reduction in plasma glucose with concomitant reduced fibroblast growth factor-19 concentrations, increased de novo synthesis of bile acids, a shift towards a more hydrophilic bile acid pool and increased lipogenesis. No glucagon-like peptide-1-mediated effects on insulin, glucagon or gastric emptying were evident, which point to limited contribution of this incretin hormone to the glucose-lowering effect of sevelamer. Furthermore, no sevelamer-mediated effects on gut microbiota composition or resting energy expenditure were observed.

CONCLUSIONS: Sevelamer reduced plasma glucose concentrations in patients with type 2 diabetes by mechanisms that seemed to involve decreased intestinal and hepatic bile acid-mediated farnesoid X receptor activation.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number7
Pages (from-to)1623-1631
Number of pages8
ISSN1462-8902
DOIs
Publication statusPublished - Jul 2018

    Research areas

  • Journal Article

ID: 52823097