Incretin Hormone Antagonism After Bariatric Surgery

Overview

Using the glucagon-like peptide-1 (GLP-1) antagonist exendin(9-39) and the glucose-dependent insulinotropic peptide (GIP) antagonist GIP(3-30), the purpose of this study is to clarify the importance of endogenous GLP-1 and GIP for postprandial glucose metabolism after RYGB and SG in subjects with normal glucose tolerance. We hypothesize that GLP-1 is more important after RYGB, and GIP is more important after SG, for postprandial glucose tolerance and beta-cell function. A group of un-operated subjects with normal glucose tolerance will serve as controls.

Full Title of Study: “Importance of Endogenous Glucagon-like Peptide-1 and Glucose-dependent Insulinotropic Polypeptide for Postprandial Glucose Metabolism After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy Surgery”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Basic Science
    • Masking: Single (Participant)
  • Study Primary Completion Date: April 16, 2021

Interventions

  • Other: Placebo
    • Four-hour liquid mixed meal tests and a subsequent ad libitum meal during saline infusion.
  • Other: GLP-1 antagonism
    • Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin 9-39 and saline infusion.
  • Other: GIP antagonism
    • Four-hour liquid mixed meal tests and a subsequent ad libitum meal during GIP(3-30) and saline infusion.
  • Other: GLP-1 and GIP antagonism
    • Four-hour liquid mixed meal tests and a subsequent ad libitum meal during exendin and GIP(3-30) infusion.

Arms, Groups and Cohorts

  • Other: Gastric bypass operated patients
    • Four test days in a randomized, patient-blinded, cross-over design
  • Other: Sleeve gastrectomy operated patients
    • Four test days in a randomized, patient-blinded cross-over, design
  • Other: Un-operated controls
    • Four test days in a randomized, patient-blinded cross-over, design

Clinical Trial Outcome Measures

Primary Measures

  • iAUC glucose
    • Time Frame: 240 minutes
    • Main comparison between groups: delta iAUC glucose (iAUC exendin(9-39) test day – iAUC GIP(3-30) test day) in the RYGB group compared to the SG group

Secondary Measures

  • Beta-cell glucose sensitivity (β-GS)
    • Time Frame: 240 minutes
    • Main comparison between groups: delta β-GS (β-GS exendin(9-39) test day – β-GS GIP(3-30) test day) in the RYGB group compared to the SG group

Participating in This Clinical Trial

Inclusion Criteria, surgery groups:

  • Age > 18 years – RYGB or SG operation > 12 months prior to inclusion – Weight stable (± 3 kg during the last month) – HbA1c < 48 mmol/mol before surgery, and no history of diabetes – HbA1c < 48 mmol/mol and fasting plasma glucose < 6.1 mmol/l at inclusion Inclusion Criteria, control group: – Age > 18 years – no former RYGB- or SG operation – Weight stable (± 3 kg during the last month) – HbA1c < 48 mmol/mol, fasting plasma glucose < 6.1 mmol/l and no history of diabetes Exclusion Criteria:

  • Thyrotoxicosis or inadequately treated hypothyreosis – Hemoglobin < 6.5 mmol/l at inclusion – Pregnancy or breast feeding – Medication affecting the planned examinations Matching between groups – Age – Sex – BMI at inclusion and for surgery groups also pre-surgery BMI

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Hvidovre University Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Morten Gadegaard Hindsø, MD, Principal Investigator – Hvidovre University Hospital
  • Overall Official(s)
    • Kirstine N Bojsen-Møller, MD, PHD, Principal Investigator, Dept. of Endocrinology, Hvidovre Hospital, Denmark
    • Morten G Hindsø, MD, Principal Investigator, Dept. of Endocrinology, Hvidovre Hospital, Denmark

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