Effects of Sitagliptin on Gastric Emptying, Glycaemia and Blood Pressure in Type 2 Diabetes

Overview

The purpose of this study is to evaluate the acute effects of sitagliptin on postprandial glycemia, incretin hormones and blood pressure, and the relationship to gastric emptying, after a mashed potato meal in patients with type 2 diabetes.

Full Title of Study: “Effects of Sitagliptin on Postprandial Glycaemia, Incretin Hormones and Blood Pressure in Type 2 Diabetes – Relationship to Gastric Emptying”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: January 2017

Detailed Description

The purpose of this study is to (i) evaluate the acute effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin (100mg once daily for two days), on gastric emptying, postprandial plasma glucose, insulin, glucagon and 'incretin' hormones (ie. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)), blood pressure and heart rate after a high carbohydrate meal, and (ii) to determine whether the magnitude of the effects of sitagliptin on postprandial glycaemia and blood pressure is related to the rate of gastric emptying, in patients with type 2 diabetes.

The rate of entry of carbohydrate into the small intestine is especially important in patients with diabetes mellitus. Sitagliptin is an orally administered inhibitor of dipeptidyl-peptidase-IV (DPP-IV), the enzyme responsible for the degradation of GLP-1. It is hypothesized that sitagliptin will increase the GLP-1 response to, and thereby slow gastric emptying and diminish the glycaemic and blood pressure response to, a carbohydrate-containing meal.

Twenty healthy subjects (male and female) will be studied. Each subject will be studied on two occasions following treatment for 2 days with sitagliptin (100mg once daily) or matching placebo in a randomized, double blind, crossover design. Measurements of gastric emptying, intragastric meal distribution, blood glucose concentrations, gut hormones, blood pressure, splanchnic flow and appetite will be measured for 4 hours following ingestion of a mashed potato meal.

Interventions

  • Drug: Sitagliptin
    • 100mg mane for 2 days
  • Drug: Placebo
    • Inactive drug (Placebo)

Arms, Groups and Cohorts

  • Experimental: Sitaglipltin (100mg)
    • Active drug (sitagliptin)
  • Placebo Comparator: Placebo (sugar pill)
    • Inactive drug (placebo)

Clinical Trial Outcome Measures

Primary Measures

  • Gastric emptying
    • Time Frame: 3 hours per gastric emptying study (i.e. 6 hours)
    • Gastric retention (percent in the total stomach)

Secondary Measures

  • Glycaemia
    • Time Frame: 4 hours during each gastric empty study (i.e. 8 hours)
    • blood glucose (mmol/L) and plasma insulin (mU/L)
  • Gastrointestinal hormone release
    • Time Frame: 4 hours during each gastric empty study (i.e. 8 hours)
    • GLP-1, GIP, C-peptide, 3-OMG
  • Intragastric meal distribution
    • Time Frame: 3 hours during each gastric empty study (i.e. 6 hours)
    • percent retention in the proximal and distal stomach
  • Blood pressure
    • Time Frame: 4.5 hours during each gastric empty study (i.e. 9 hours)
    • systolic and diastolic blood pressure (mmHg)
  • Heart rate
    • Time Frame: 4.5 hours during each gastric empty study (i.e. 9 hours)
    • Heart rate (beats per minute)
  • Splanchnic blood flow
    • Time Frame: 4 hours during each gastric empty study (i.e. 8 hours)
    • Doppler ultrasound of superior mesenteric artery flow (ml/min)
  • Cardiac output
    • Time Frame: 4 hours during each gastric empty study (i.e. 8 hours)
    • Finapres (L)
  • Stroke volume
    • Time Frame: 4 hours during each gastric empty study (i.e. 8 hours)
    • Finapres (mL)
  • Appetite
    • Time Frame: 4 hours during each gastric empty study (i.e. 8 hours)
    • visual analogue questionnaire to assess hunger, fullness, desire to eat (mm)

Participating in This Clinical Trial

Inclusion Criteria

  • Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin alone
  • Body mass index (BMI) 20 – 40 kg/m2
  • Males and females (females of reproductive potential must be using an appropriate contraceptive method)
  • Glycated haemoglobin (HbA1c) ≤ 8.5%
  • Haemoglobin above the lower limit of the normal range (i.e. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. >10mcg/L)

Exclusion Criteria

  • Subjects with gastrointestinal disease, significant upper or lower gastrointestinal symptoms, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy)
  • Other significant illness, including epilepsy, cardiovascular or respiratory disease.
  • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy.
  • Impaired renal or liver function (as assessed by calculated creatinine clearance < 50 mL/min using the Cockroft-Gault equation (27) or abnormal liver function tests (> 2 times upper limit of normal range)).
  • Requirement for medication known to influence blood pressure and/or heart rate and/or gastrointestinal function, drugs with anticholinergic effects
  • Alcohol consumption > 20 g per day
  • Smoking > 10 cigarettes per day
  • Pregnancy or lactation.
  • Vegetarian
  • Allergy to sitagliptin or any other 'gliptin'.
  • Donation of blood within the previous 3 months
  • Participation in any other research studies within the previous 3 months
  • Exposure to ionising radiation for research purposes in the previous 12 months
  • Inability to give informed consent

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Royal Adelaide Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Karen Jones, Professor – Royal Adelaide Hospital
  • Overall Official(s)
    • Karen L Jones, DAppSci, PhD, Principal Investigator, University of Adelaide

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