Evidence map›Paper›PMID 32344198›Full record

Trial reportEBioMedicine2020

Ileo-colonic delivery of conjugated bile acids improves glucose homeostasis via colonic GLP-1-producing enteroendocrine cells in human obesity and diabetes.

Gerardo Calderon, Alison McRae, Juraj Rievaj, Judith Davis, Inuk Zandvakili, Sara Linker-Nord, Duane Burton, Geoffrey Roberts, Frank Reimann, Bronislava Gedulin and 5 more

Erratum issued 2 registry-linked trialsOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
5.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02033876 phase2completednot on this map

Effect of Delayed-Release Ursodeoxycholic Acid on Insulin Sensitivity, Gastric Emptying and Body Weight in Overweight or Obese Patients With Type 2 Diabetes on Metformin Treatment

TypeinterventionalSponsorMayo ClinicRan2013 to 2017Enrolled24ConditionsType 2 Diabetes MellitusArmsUrsodiol
NCT02871882 phase2completednot on this map

Effect of Delayed-Release Bile Acid on Insulin Sensitivity, Gastric Emptying and Body Weight in Overweight or Obese Patients With Type 2 Diabetes Mellitus

TypeinterventionalSponsorMayo ClinicRan2016 to 2017Enrolled24ConditionsType 2 Diabetes Mellitus, Obese, OverweightArmsGastric Emptying test, Mixed Oral Glucose Tolerance test, Conjugated bile acids sodium, Placebo
3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 75 citations in OpenAlex.

  1. Trial
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  3. DuodenalGut · 2022
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  6. Article
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  13. Article
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  16. Bile acids as therapeutic agents.Frontiers in pharmacology · 2025
    Review
  17. Review
  18. Review
  19. Pharmaceuticals (Basel, Switzerland) · 2024
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

Gerardo CalderonClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Alison McRaeClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Juraj RievajUniversity of Cambridge, UK; Current affiliation: Dosage Form Design & Development, AstraZeneca Granta Park, Cambridge CB21 6GH, UK.
Judith DavisClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Inuk ZandvakiliClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Sara Linker-NordClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Duane BurtonClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Geoffrey RobertsCurrent affiliation: Dosage Form Design & Development, AstraZeneca Granta Park, Cambridge CB21 6GH, UK.
Frank ReimannUniversity of Cambridge, UK.
Bronislava GedulinSatiogen Pharmaceuticals, San Diego, CA, United States.
Adrian VellaDivision of Endocrinology, Department of Medicine, Mayo Clinic, Rochester, MN, United States.
Nicholas F LaRussoClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Michael CamilleriClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States.
Fiona M GribbleUniversity of Cambridge, UK.
Andres AcostaClinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Charlton 8-142, 200 First St. S.W., Rochester, MN 55905, United States. Electronic address: acosta.andres@mayo.edu.
Mayo Clinic · USAstraZeneca (United Kingdom) · GBUniversity of Cambridge · GBMayo Clinic in Arizona · US

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2M
Pathophysiology of Biliary DiseaseR01DK057993 · NIDDK · MAYO CLINIC ROCHESTER · PI LARUSSO, NICHOLAS F., O'HARA, STEVEN P · 2001 to 2025
$7.1M
Pharmacogenomics of Gastric Function &Weight in ObesityR01DK067071 · NIDDK · MAYO CLINIC ROCHESTER · PI CAMILLERI, MICHAEL L. · 2004 to 2020
$4.7M
Mechanisms of Enteroendocrine L-Cell Dysfunction and Bile Adaptations to Weight LossK23DK114460 · NIDDK · MAYO CLINIC ROCHESTER · PI ACOSTA, ANDRES J · 2018 to 2022
$980k
Medical Research Council MC_UU_00014/3Medical Research Council MC_UU_12012/3NCATS NIH HHS UL1 TR000135NIDDK NIH HHS K23 DK114460NIDDK NIH HHS P30 DK084567NIDDK NIH HHS R01 DK057993NIDDK NIH HHS R01 DK067071
6 · The paper itself

Abstract

backgroundThe bile acid (BA) pathway plays a role in regulation of food intake and glucose metabolism, based mainly on findings in animal models. Our aim was to determine whether the BA pathway is altered and correctable in human obesity and diabetes.

methodsWe conducted 3 investigations: 1) BA receptor pathways were studied in NCI-H716 enteroendocrine cell (EEC) line, whole human colonic mucosal tissue and in human colonic EEC isolated by Fluorescence-activated Cell Sorting (ex vivo) from endoscopically-obtained biopsies colon mucosa; 2) We characterized the BA pathway in 307 participants by measuring during fasting and postprandial levels of FGF19, 7αC4 and serum BA; 3) In a placebo-controlled, double-blind, randomised, 28-day trial, we studied the effect of ileo-colonic delivery of conjugated BAs (IC-CBAS) on glucose metabolism, incretins, and lipids, in participants with obesity and diabetes.

findingsHuman colonic GLP-1-producing EECs express TGR5, and upon treatment with bile acids in vitro, human EEC differentially expressed GLP-1 at the protein and mRNA level. In Ussing Chamber, GLP-1 release was stimulated by Taurocholic acid in either the apical or basolateral compartment. FGF19 was decreased in obesity and diabetes compared to controls. When compared to placebo, IC-CBAS significantly decreased postprandial glucose, fructosamine, fasting insulin, fasting LDL, and postprandial FGF19 and increased postprandial GLP-1 and C-peptide. Increase in faecal BA was associated with weight loss and with decreased fructosamine. INTERPRETATIONS: In humans, BA signalling machinery is expressed in colonic EECs, deficient in obesity and diabetes, and when stimulated with IC-CBAS, improved glucose homeostasis. ClinicalTrials.gov number, NCT02871882, NCT02033876.

fundingResearch support and drug was provided by Satiogen Pharmaceuticals (San Diego, CA). AA, MC, and NFL report grants (AA- C-Sig P30DK84567, K23 DK114460; MC- NIH R01 DK67071; NFL- R01 DK057993) from the NIH. JR was supported by an Early Career Grant from Society for Endocrinology.

Indexed as

Administration, OralBile Acids and SaltsBiological TransportBlood GlucoseCapsulesCell LineCholestenonesColonDiabetes Mellitus, Type 2Diffusion Chambers, CultureEnteroendocrine CellsFastingFibroblast Growth FactorsFructosamineGene ExpressionGlucagon-Like Peptide 1Bile Acids and SaltsBlood GlucoseCapsulesCholestenonesFGF19 protein, humanFibroblast Growth FactorsFructosamineGlucagon-Like Peptide 1GPBAR1 protein, humanInsulinReceptors, G-Protein-Coupled

Identifiers

PMID32344198
PMCPMC7186521
OpenAlexW3018630251

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.