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Trial · Interventional

CompletedPhase 4Registry data

SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

NCTNCT01744236 (opens ClinicalTrials.gov in a new tab)Other idDC2012SAFE001Other idU1111-1130-8248Other id2012-003256-36
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 4
Enrollment
70 participants (actual)
Sponsor
Amsterdam UMC, location VUmc · Other
Design
Randomized · Double masking
Countries
1 country

Netherlands

Start
Apr 2013
Primary completion
Aug 2015
Completion
Aug 2015
First posted
6 Dec 2012 (estimated)
Last update posted
9 Dec 2015 (estimated)
Conditions
Type 2 Diabetes

Timeline

1 trial · 1 completed

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2013201420152016
  1. Ph 4

    SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

    NCT01744236

    Apr 2013 to Aug 2015

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The aim of this study is to detail the (mechanisms underlying the) actions of the GLP-1 receptor agonists and DPP-4 inhibitors on the cardiovascular, renal and gastrointestinal systems in patients with Type 2 Diabetes Mellitus.

Interventions

  • LiraglutideDrug
  • SitagliptinDrug
  • ExenatideDrug
  • Liraglutide placeboDrug
  • Sitagliptin placeboDrug
  • Exenatide placeboDrug
  • L-NMMADrug

Arms7

  • Experimental

    Liraglutide (main study, long-term intervention)

    This arm (n=20) will receive liraglutide 1.8mg and sitagliptin-placebo during 12 weeks

  • Experimental

    Sitagliptin (main study, long-term intervention)

    This arm (n=20) will receive sitagliptin 100mg and liraglutide-placebo during 12 weeks

  • Placebo comparator

    Placebo (main study, long-term intervention)

    This arm (n=20) will receive liraglutide-placebo and sitagliptin-placebo during 12 weeks

  • Experimental

    Exenatide (main study, acute intervention)

    Prior to the 12-week intervention study, a GLP-1 receptor agonist (exenatide) will be administered intravenously (n=30).

  • Placebo comparator

    Placebo (main study, acute intervention)

    Prior to the 12-week intervention study, placebo will be administered intravenously (n=30).

  • Other

    Acute MRI intervention study

    In a subset of 12 patients with type 2 diabetes, a crossover trial with acute infusion of exenatide and placebo is performed. This is done prior to the 12-week intervention study.

  • Other

    Pilot-study

    In 10 healthy obese subjects, a crossover trial with acute infusion of exenatide, placebo and L-NMMA is performed.

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. Changes from baseline following infusion of GLP-1RA (acute effects) and the changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on resting heart rate variability, as derived from electrocardiographic measurements.

    Time frame · 12 weeks

  2. Changes from baseline following infusion of GLP-1RA (acute effects) and the changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on Glomerular Filtration Rate, measured by the inulin-clearance technique.

    Time frame · 12 weeks

  3. Changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on pancreatic exocrine function, measured as fecal Elastase-1.

    Time frame · 12 weeks

Secondary outcomes(3)

  1. Changes from baseline following infusion of GLP-1RA (acute effects) and the changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on the following cardiovascular parameters:

    Time frame · 12 weeks

    Registry description

    * Blood pressure and heart rate * Hemodynamic variables (blood pressure, heart rate, stroke volume, cardiac output/-index/-contractility, systemic vascular resistance) derived from non-invasive beat-to-beat finger blood pressure measurements * Cardiac autonomic nervous system function * Microvascular function and vasomotion * Arterial stiffness * Lipid spectrum * Glycemic variables (HbA1c, fasting and postprandial glucose) * Body anthropometrics: body weight, height, BMI and waist circumference * Body fat content

  2. Changes from baseline following infusion of GLP-1RA (acute effects) and the changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on the following renal parameters:

    Time frame · 12 weeks

    Registry description

    * Effective renal plasma flow (ERPF) * Renal tubular function * Renal damage, measured by urine biomarkers

  3. Changes from baseline following infusion of GLP-1RA (acute effects*) and changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on the following gastrointestinal parameters:

    Time frame · 12 weeks

    Registry description

    * Pancreatic exocrine function (\* In the acute intervention only exocrine pancreatic function is assessed) * Pancreatic structure * Pancreatic enzymes * Gallbladder emptying speed * Liver enzymes * Hepatic structure/steatosis * Gastric emptying

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

Completed trials do not always post results.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies6

Studies that cite this trial.

Studies with results

4 studies on this page

Indexing hint: Randomized controlled trial · 2021

6 results

Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes.

Smits et al. 2021Diabetes & metabolismcited by 59

PMID 33429063DOI 10.1016/j.diabet.2021.101223PUB-33429063

CC BY6 results
Download PDFSee results (6)

Indexing hint: Randomized controlled trial · 2016

19 results

Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial.

Tonneijck et al. 2016Diabetologiacited by 109

PMID 27038451PMC4901099DOI 10.1007/s00125-016-3938-zPUB-27038451

CC BY19 results
Download PDFSee results (19)

Indexing hint: Randomized controlled trial · 2016

5 results

Biliary effects of liraglutide and sitagliptin, a 12-week randomized placebo-controlled trial in type 2 diabetes patients.

Smits et al. 2016Diabetes, obesity & metabolismcited by 50

PMID 27451030PMC5129471DOI 10.1111/dom.12748PUB-27451030

Free to read · publisher termsCC BY-NC5 results
Read at sourceSee results (5)

Indexing hint: Randomized controlled trial · 2016

4 results

Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial.

Smits et al. 2016Diabetologiacited by 118

PMID 27627981PMC6518065DOI 10.1007/s00125-016-4100-7PUB-27627981

CC BY4 results
Download PDFSee results (4)

Indexing hint: Randomized controlled trial · 2015

Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes.

Smits et al. 2015BMJ opencited by 28

PMID 26586327PMC4654309DOI 10.1136/bmjopen-2015-009579PUB-26586327

Free to read · publisher termsCC BY-NC
Read at source

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2016

Corrected

Renal Effects of DPP-4 Inhibitor Sitagliptin or GLP-1 Receptor Agonist Liraglutide in Overweight Patients With Type 2 Diabetes: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

Tonneijck et al. 2016Diabetes carecited by 85

PMID 27585605DOI 10.2337/dc16-1371PUB-27585605

Full text at the publisher
Publisher pageRead the notice

Eligibility

Who could join, as posted.

Sex
All
Age
from 35 Years up to 75 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Age between 35 and 75 years. * Females must be post-menopausal (no menses \>1 year). * Type 2 diabetes (HbA1c 6.5-9% DCCT or 48-75 mmol/mol IFCC), who are being treated with a stable dose of oral antihyperglycemic agents (either metformin alone, SU alone or a combination of metformin and SU) for at least 3 months prior to inclusion. * BMI 25 - 40 kg/m2 * Caucasian * Signed informed consent Exclusion Criteria: * GFR \< 60 mL/min/1.73m2 * Current / chronic use of the following medication: thiazolidinediones, GLP-1RA, DPP-4i, glucocorticoids, NSAIDs, insulin, antimicrobial agents, chemotherapeutics or immune suppressants. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study. * History of or actual pancreatic disease or impaired pancreatic exocrine function * Active liver disease * History of or actual malignancy (with the exception of basal cell carcinoma) * Current urinary tract infection and active nephritis * Recent (\<6 months) history of cardiovascular disease, including acute coronary syndrome, stroke, transient ischemic neurologic disorder or chronic heart failure (New York Heart Association grade II-IV) * Current atrial fibrillation * Chronic infectious or auto-immune disease * Substance and/or alcohol abuse * History of allergy/hypersensitivity to any of the test agents * Complaints compatible with or established gastroparesis and/or neurogenic bladder * Any condition that has been recognized as a contra-indication for the use of GLP-1RA and DPP-4i, as listed in the respective SPCs * History of or actual (severe) mental illness * Inability to understand the study protocol and/or inability to give informed consent * History of claustrophobia or presence of metal objects/implants (because of MRI protocol) For the preceding Pilot study, we will include: * Males * Age between 18 and 50 years * BMI 25 - 40 kg/m2 * Caucasian The exclusion criteria for the preceding pilot study are similar to the exclusion criteria of the main study, with the additions of: * Subjects with a fasting plasma glucose ≥5.6 mmol/L, a 2-hour glucose of ≥7.8 mmol/L after a 75-grams oral glucose tolerance test, or a HbA1c of ≥6.5% * Subjects using any kind of medication

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