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The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction

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Title: The metabolomic effects of tripeptide gut hormone infusion compared to Roux-en-Y gastric bypass and caloric restriction
Authors: Sands, C
Alexiadou, K
Minnion, J
Tharakan, G
Behary, P
Ahmed, A
Purkayastha, S
Lewis, M
Bloom, S
Li, J
Tan, T
Item Type: Journal Article
Abstract: Context: The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are regulators of energy intake and glucose homeostasis, and are thought to contribute to the glucose-lowering effects of bariatric surgery. Objective: To establish the metabolomic effects of a combined infusion of GLP-1, OXM and PYY (tripeptide “GOP”) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). Design and setting: Sub-analysis of a single-blind, randomised, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups. Patients and interventions: 25 obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n=14) or 0.9% saline control (SAL; n=11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery. Main outcome measures: Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modelling approaches to identify similarities and differences between the effects of each intervention. Results: Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB. Conclusions: Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.
Issue Date: Feb-2022
Date of Acceptance: 13-Aug-2021
URI: http://hdl.handle.net/10044/1/91275
DOI: 10.1210/clinem/dgab608
ISSN: 0021-972X
Publisher: Endocrine Society
Start Page: e767
End Page: e782
Journal / Book Title: Journal of Clinical Endocrinology and Metabolism
Volume: 107
Issue: 2
Copyright Statement: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Medical Research Council (MRC)
National Institute for Health Research
Imperial College Healthcare NHS Trust
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Medical Research Council (MRC)
Commission of the European Communities
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
The Academy of Medical Sciences
Society for Endocrinology
European Foundation for the Study of Diabetes
British Society for Neuroendocrinology
Eli Lilly & Company (USA)
Ureka Pharma SAS
Funder's Grant Number: MR/K02115X/1
RDA11 79560
RDC06 79560
RDA29
NIHR130639
MR/P002536/1
715662
RDA05 79560
MR/R010676/1
RDA29
RDC04
N/A
N/A
98102
N/A
PA1602
PA1721
Keywords: GLP-1
PYY
bariatric surgery
caloric restriction
metabolomics
oxyntomodulin
Endocrinology & Metabolism
1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
Publication Status: Published
Online Publication Date: 2021-08-30
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons