Type 2 DiabetesPhase 4NCT01744236
SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies
A Phase 4 study testing Liraglutide, Sitagliptin and Exenatide in people with Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 35 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Liraglutide, Sitagliptin and Exenatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2013to Aug 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IV, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Assess the Effect of 12-week Treatment With the Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA) Liraglutide or Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Sitagliptin on the Cardiovascular, Renal and Gastrointestinal System in Insulin-naïve Patients With Type 2 Diabetes (T2DM).
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.
Read the detailed description
GLP-1 receptors are present in most organ systems of the human body, and pharmacological interventions enhancing GLP-1 activity may influence the function of these organs. The use of GLP-1 receptor agonists (GLP-1RA) and DPP-4 inhibitors (DPP-4i) has been associated with an increased heart rate, acute pancreatitis and acute renal failure. To date, studies in humans detailing the effects of these drugs on these organ systems, biological processes and underlying mechanisms, which could explain these associations, are lacking.
Therefore, as part of the EU-FP7 SAFEGUARD program, the present study will aim to detail the (mechanisms underlying the) actions of GLP-1RA and DPP-4i on the cardiovascular, renal and gastrointestinal system in healthy obese subjects and patients with T2DM.
In the main study, sixty patients with type 2 diabetes will undergo two interventions within the same protocol in order to assess changes in the outcome parameters:
- acute study = acute infusion with exenatide or placebo (to assess the cardiovascular and renal effects)
- long-term study = 12 weeks of treatment with liraglutide, sitagliptin or placebo (to assess the cardiovascular, renal and gastrointestinal effects)
In a substudy (termed 'acute MRI study'), twelve patients with type 2 diabetes will undergo an additional acute intervention study with exenatide (to assess the pancreatic effects)
In a substudy (termed 'pilot-study'), ten healthy obese subjects will undergo a similar acute study like the patients with type 2 diabetes (to assess the cardiovascular and renal effects). Moreover, in these healthy subjects, the effects of exenatide during L-NMMA infusion will be assessed.
- Conditions
- Type 2 Diabetes
- Being tested
- Liraglutide, Sitagliptin, Exenatide, Liraglutide placebo, Sitagliptin placebo
- Keywords
- GLP-1 Receptor Agonists, DPP-4 inhibitors
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Liraglutide will be started with a titration period of 2 weeks (week 1: 0.6mg once daily and week 2: 1.2mg once daily). If liraglutide is well tolerated it will be continued for 10 more weeks in a dosage of 1.8mg once daily.
SitagliptinDrug
Sitagliptin 100mg will be given once daily for 12 weeks.
ExenatideDrug
Exenatide will be administered intravenously with a loading dose of 50ng/min for 30 minutes, followed by a maintenance dose of 25ng/min during the rest of the tests
Liraglutide placeboDrug
Liraglutide-placebo will be started with a titration period of 2 weeks (week 1: 0.6mg once daily and week 2: 1.2mg once daily). It will be continued for 10 more weeks in a dosage of 1.8mg once daily.
Sitagliptin placeboDrug
Sitagliptin-placebo be given once daily for 12 weeks.
Exenatide placeboDrug
Exenatide-placebo (saline) will be administered intravenously
L-NMMADrug
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide (main study, long-term intervention) | Experimental | This arm (n=20) will receive liraglutide 1.8mg and sitagliptin-placebo during 12 weeks Receives: Drug: Liraglutide; Drug: Sitagliptin placebo |
| Sitagliptin (main study, long-term intervention) | Experimental | This arm (n=20) will receive sitagliptin 100mg and liraglutide-placebo during 12 weeks Receives: Drug: Sitagliptin; Drug: Liraglutide placebo |
| Placebo (main study, long-term intervention) | Placebo comparator | This arm (n=20) will receive liraglutide-placebo and sitagliptin-placebo during 12 weeks Receives: Drug: Liraglutide placebo; Drug: Sitagliptin placebo |
| Exenatide (main study, acute intervention) | Experimental | Prior to the 12-week intervention study, a GLP-1 receptor agonist (exenatide) will be administered intravenously (n=30). Receives: Drug: Exenatide |
| Placebo (main study, acute intervention) | Placebo comparator | Prior to the 12-week intervention study, placebo will be administered intravenously (n=30). Receives: Drug: Exenatide placebo |
| Acute MRI intervention study | Other | 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. Receives: Drug: Exenatide; Drug: Exenatide placebo |
| Pilot-study | Other | In 10 healthy obese subjects, a crossover trial with acute infusion of exenatide, placebo and L-NMMA is performed. Receives: Drug: Exenatide; Drug: Exenatide placebo; Drug: L-NMMA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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.
Measured: 12 weeks
Secondary outcomes (3)
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:
- 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
Measured: 12 weeks
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:
- Effective renal plasma flow (ERPF)
- Renal tubular function
- Renal damage, measured by urine biomarkers
Measured: 12 weeks
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:
- 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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study startApr 2013
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- EU FP7: SAFEGUARD consortium
- Responsible party
- Principal investigator, M.H.H. Kramer, Amsterdam UMC, location VUmc
- Investigators
- M.H.H. Kramer, MD PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01744236
- Sponsor's protocol ID
- DC2012SAFE001
- Other IDs
- U1111-1130-8248, 2012-003256-36
- Status last verified
- Dec 2015
- First submitted
- 4 Dec 2012
- Last updated
- 9 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Smits MM, Fluitman KS, Herrema H, Davids M, Kramer MHH, Groen AK, Belzer C, de Vos WM, Cahen DL, Nieuwdorp M, van Raalte DH. Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes. Diabetes Metab. 2021 Sep;47(5):101223. doi: 10.1016/j.diabet.2021.101223. Epub 2021 Jan 8.
PubMed 33429063Smits MM, Tonneijck L, Muskiet MH, Kramer MH, Pouwels PJ, Pieters-van den Bos IC, Hoekstra T, Diamant M, van Raalte DH, Cahen DL. Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial. Diabetologia. 2016 Dec;59(12):2588-2593. doi: 10.1007/s00125-016-4100-7. Epub 2016 Sep 15.
PubMed 27627981Tonneijck L, Smits MM, Muskiet MH, Hoekstra T, Kramer MH, Danser AH, Ter Wee PM, Diamant M, Joles JA, van Raalte DH. 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. Diabetes Care. 2016 Nov;39(11):2042-2050. doi: 10.2337/dc16-1371. Epub 2016 Sep 1.
PubMed 27585605Smits MM, Tonneijck L, Muskiet MH, Hoekstra T, Kramer MH, Diamant M, Nieuwdorp M, Groen AK, Cahen DL, van Raalte DH. Biliary effects of liraglutide and sitagliptin, a 12-week randomized placebo-controlled trial in type 2 diabetes patients. Diabetes Obes Metab. 2016 Dec;18(12):1217-1225. doi: 10.1111/dom.12748. Epub 2016 Aug 30.
PubMed 27451030Tonneijck L, Smits MM, Muskiet MHA, Hoekstra T, Kramer MHH, Danser AHJ, Diamant M, Joles JA, van Raalte DH. Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial. Diabetologia. 2016 Jul;59(7):1412-1421. doi: 10.1007/s00125-016-3938-z. Epub 2016 Apr 1.
PubMed 27038451Smits MM, Tonneijck L, Muskiet MH, Hoekstra T, Kramer MH, Pieters IC, Cahen DL, Diamant M, van Raalte DH. 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. BMJ Open. 2015 Nov 19;5(11):e009579. doi: 10.1136/bmjopen-2015-009579.
PubMed 26586327
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Assess the Effect of 12-week Treatment With the Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA) Liraglutide or Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Sitagliptin on the Cardiovascular, Renal and Gastrointestinal System in Insulin-naïve Patients With Type 2 Diabetes (T2DM).
- ClinicalTrials.gov ID
- NCT01744236
- Acronym / sponsor ID
- DC2012SAFE001
- Conditions
- Type 2 Diabetes
- Keywords
- GLP-1 Receptor Agonists, DPP-4 inhibitors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- EU FP7: SAFEGUARD consortium
- Study start
- Apr 2013
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 6 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
GLP-1 receptors are present in most organ systems of the human body, and pharmacological interventions enhancing GLP-1 activity may influence the function of these organs. The use of GLP-1 receptor agonists (GLP-1RA) and DPP-4 inhibitors (DPP-4i) has been associated with an increased heart rate, acute pancreatitis and acute renal failure. To date, studies in humans detailing the effects of these drugs on these organ systems, biological processes and underlying mechanisms, which could explain these associations, are lacking.
Therefore, as part of the EU-FP7 SAFEGUARD program, the present study will aim to detail the (mechanisms underlying the) actions of GLP-1RA and DPP-4i on the cardiovascular, renal and gastrointestinal system in healthy obese subjects and patients with T2DM.
In the main study, sixty patients with type 2 diabetes will undergo two interventions within the same protocol in order to assess changes in the outcome parameters:
- acute study = acute infusion with exenatide or placebo (to assess the cardiovascular and renal effects)
- long-term study = 12 weeks of treatment with liraglutide, sitagliptin or placebo (to assess the cardiovascular, renal and gastrointestinal effects)
In a substudy (termed 'acute MRI study'), twelve patients with type 2 diabetes will undergo an additional acute intervention study with exenatide (to assess the pancreatic effects)
In a substudy (termed 'pilot-study'), ten healthy obese subjects will undergo a similar acute study like the patients with type 2 diabetes (to assess the cardiovascular and renal effects). Moreover, in these healthy subjects, the effects of exenatide during L-NMMA infusion will be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Liraglutide (main study, long-term intervention) | Experimental | Drug: Liraglutide, Drug: Sitagliptin placeboThis arm (n=20) will receive liraglutide 1.8mg and sitagliptin-placebo during 12 weeks |
| Sitagliptin (main study, long-term intervention) | Experimental | Drug: Sitagliptin, Drug: Liraglutide placeboThis arm (n=20) will receive sitagliptin 100mg and liraglutide-placebo during 12 weeks |
| Placebo (main study, long-term intervention) | Placebo comparator | Drug: Liraglutide placebo, Drug: Sitagliptin placeboThis arm (n=20) will receive liraglutide-placebo and sitagliptin-placebo during 12 weeks |
| Exenatide (main study, acute intervention) | Experimental | Drug: ExenatidePrior to the 12-week intervention study, a GLP-1 receptor agonist (exenatide) will be administered intravenously (n=30). |
| Placebo (main study, acute intervention) | Placebo comparator | Drug: Exenatide placeboPrior to the 12-week intervention study, placebo will be administered intravenously (n=30). |
| Acute MRI intervention study | Other | Drug: Exenatide, Drug: Exenatide placeboIn 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. |
| Pilot-study | Other | Drug: Exenatide, Drug: Exenatide placebo, Drug: L-NMMAIn 10 healthy obese subjects, a crossover trial with acute infusion of exenatide, placebo and L-NMMA is performed. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (24 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiraglutideLiraglutide will be started with a titration period of 2 weeks (week 1: 0.6mg once daily and week 2: 1.2mg once daily). If liraglutide is well tolerated it will be continued for 10 more weeks in a dosage of 1.8mg once daily. | Drug | Liraglutide (main study, long-term intervention) |
| SitagliptinSitagliptin 100mg will be given once daily for 12 weeks. | Drug | Sitagliptin (main study, long-term intervention) |
| ExenatideExenatide will be administered intravenously with a loading dose of 50ng/min for 30 minutes, followed by a maintenance dose of 25ng/min during the rest of the tests | Drug | Acute MRI intervention study, Exenatide (main study, acute intervention), Pilot-study |
| Liraglutide placeboLiraglutide-placebo will be started with a titration period of 2 weeks (week 1: 0.6mg once daily and week 2: 1.2mg once daily). It will be continued for 10 more weeks in a dosage of 1.8mg once daily. | Drug | Placebo (main study, long-term intervention), Sitagliptin (main study, long-term intervention) |
| Sitagliptin placeboSitagliptin-placebo be given once daily for 12 weeks. | Drug | Liraglutide (main study, long-term intervention), Placebo (main study, long-term intervention) |
| Exenatide placeboExenatide-placebo (saline) will be administered intravenously | Drug | Acute MRI intervention study, Pilot-study, Placebo (main study, acute intervention) |
| L-NMMA | Drug | Pilot-study |
Primary outcome
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
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
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
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2015.
- Derived from this study: PubMed 33429063Smits MM, Fluitman KS, Herrema H, Davids M, Kramer MHH, Groen AK, Belzer C, de Vos WM, Cahen DL, Nieuwdorp M, van Raalte DH. Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes. Diabetes Metab. 2021 Sep;47(5):101223. doi: 10.1016/j.diabet.2021.101223. Epub 2021 Jan 8.
- Derived from this study: PubMed 27627981Smits MM, Tonneijck L, Muskiet MH, Kramer MH, Pouwels PJ, Pieters-van den Bos IC, Hoekstra T, Diamant M, van Raalte DH, Cahen DL. Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial. Diabetologia. 2016 Dec;59(12):2588-2593. doi: 10.1007/s00125-016-4100-7. Epub 2016 Sep 15.
- Derived from this study: PubMed 27585605Tonneijck L, Smits MM, Muskiet MH, Hoekstra T, Kramer MH, Danser AH, Ter Wee PM, Diamant M, Joles JA, van Raalte DH. 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. Diabetes Care. 2016 Nov;39(11):2042-2050. doi: 10.2337/dc16-1371. Epub 2016 Sep 1.
- Derived from this study: PubMed 27451030Smits MM, Tonneijck L, Muskiet MH, Hoekstra T, Kramer MH, Diamant M, Nieuwdorp M, Groen AK, Cahen DL, van Raalte DH. Biliary effects of liraglutide and sitagliptin, a 12-week randomized placebo-controlled trial in type 2 diabetes patients. Diabetes Obes Metab. 2016 Dec;18(12):1217-1225. doi: 10.1111/dom.12748. Epub 2016 Aug 30.
- Derived from this study: PubMed 27038451Tonneijck L, Smits MM, Muskiet MHA, Hoekstra T, Kramer MHH, Danser AHJ, Diamant M, Joles JA, van Raalte DH. Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial. Diabetologia. 2016 Jul;59(7):1412-1421. doi: 10.1007/s00125-016-3938-z. Epub 2016 Apr 1.
- Derived from this study: PubMed 26586327Smits MM, Tonneijck L, Muskiet MH, Hoekstra T, Kramer MH, Pieters IC, Cahen DL, Diamant M, van Raalte DH. 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. BMJ Open. 2015 Nov 19;5(11):e009579. doi: 10.1136/bmjopen-2015-009579.
Related trials for Type 2 Diabetes
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M.H.H. Kramer, MD PhD principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liraglutide, Sitagliptin and Exenatide in people with Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01744236, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2015.