Type 2 DiabetesPhase 4RENALISNCT02106104
Renal Effects of DPP-4 Inhibitor Linagliptin in Type 2 Diabetes
A Phase 4 study testing Linagliptin 5 mg QD (N=24) and Glimepiride 1 mg QD (N=24) 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 DPP-4 inhibitor linagliptin on the renal system in patients with type 2 diabetes mellitus. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Linagliptin 5 mg QD (N=24) and Glimepiride 1 mg QD (N=24)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2014to Apr 2016
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with type 2 diabetes (HbA1c: 6.5-9.0% DCCT or 48-75 mmol/mol IFCC)
- Metformin monotherapy; using a stable dose for at least 3 months prior to inclusion
- Both genders (females must be post-menopausal)
- Caucasian
- Age: 35-75 years
- Body Mass Index: >25 kg/m2
- All patients with previously diagnosed hypertension should use a RAS-interfering agent (angiotensin converting enzyme inhibitor/angiotensin II receptor blocker) for at least 3 months
Who cannot join
- Current / chronic use of the following medication: thiazolidinediones, insulin, glucocorticoids, immune suppressants, antimicrobial agents or chemotherapeutics. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study
- Chronic use of NSAIDs will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications. However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing
- Pregnancy
- Frequent occurrence of (confirmed) hypoglycemia (plasma glucose <3.9 mmol/L)
- Estimated Glomerular Filtration Rate < 60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
- Current urinary tract infection and active nephritis
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- Recent (<6 months) history of cardiovascular disease, including: acute coronary syndrome, chronic heart failure (New York Heart Association grade II-IV), stroke, transient ischemic neurologic disorder
- Complaints compatible with or established gastroparesis and/or neurogenic bladder
- Active liver disease
- History of or actual pancreatic disease
- History of or actual malignancy (except for basal cell carcinoma)
- History of or actual severe mental disease
- Substance abuse (alcohol: defined as >4 units/day; smoking/nicotine: defined as daily smoking/use)
- Allergy to any of the agents used in the study
- Inability to understand the study protocol or give informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 4, Monocenter, Randomized, Double-blind, Comparator-controlled, Parallel-group, Mechanistic Intervention Trial to Assess the Effect of 8-week Treatment With the Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Linagliptin Versus the Sulfonylurea (SU) Derivative Glimepiride on Renal Physiology and Biomarkers in Metformin-treated Patients With Type 2 Diabetes Mellitus (T2DM)
The aim of this study is to detail the (mechanisms underlying the) actions of the DPP-4 inhibitor linagliptin on the renal system in patients with type 2 diabetes mellitus.
Read the detailed description
Based on preclinical and small-sized studies in non-diabetic individuals, incretin-based therapies, i.e. glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i), may hold promise in preventing the onset and progression of diabetic kidney disease. However, the potential renoprotective effects of these agents, that are believed to be effectuated "beyond glucose control", have not been sufficiently detailed in human diabetes.
Therefore, the present study aims to explore the mechanistic and clinical effects of DPP-4i on fasting and postprandial renal physiology and biomarkers in patients with type 2 diabetes.
Forty-eight patients with type 2 diabetes will undergo an eight week intervention with linagliptin or glimepiride in order to assess changes in the outcome parameters.
- Conditions
- Type 2 Diabetes
- Being tested
- Linagliptin 5 mg QD (N=24), Glimepiride 1 mg QD (N=24)
- Keywords
- Type 2 diabetes mellitus, Diabetic kidney disease, Diabetic nephropathy, Renoprotection, DPP-4 inhibitors, Linagliptin, SU derivatives, Glimepiride
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linagliptin 5 mg QD (N=24)Drug
Also called Trajenta
Linagliptin 5 mg will be taken orally, once daily for 8 weeks
Glimepiride 1 mg QD (N=24)Drug
Also called Amaryl
Glimepiride 1 mg will be taken orally, once daily for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Linagliptin 5 mg QD (N=24) | Experimental | Linagliptin 5 mg will be taken orally, once daily for 8 weeks Receives: Drug: Linagliptin 5 mg QD (N=24) |
| Glimepiride 1 mg QD (N=24) | Active comparator | Glimepiride 1 mg will be taken orally, once daily for 8 weeks Receives: Drug: Glimepiride 1 mg QD (N=24) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline following 8-week treatment with linagliptin vs glimepiride on fasting and postprandial renal hemodynamics, measured as GFR / ERPF (determined by inulin/para-aminohippuric-acid clearance)
Measured: 8 weeks
Secondary outcomes (3)
Renal tubular function
Measured: 8 weeks
Renal damage, measured by urine biomarkers
Measured: 8 weeks
Blood Pressure and Heart Rate
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startMar 2014
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M.H.H. Kramer, Amsterdam UMC, location VUmc
- Investigators
- Mark Kramer, MD PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106104
- Sponsor's protocol ID
- DC2013RENALIS
- Other IDs
- U1111-1143-9518, 2013-002493-47, NL47157.029.13
- Acronym
- RENALIS
- Status last verified
- May 2016
- First submitted
- 28 Mar 2014
- Last updated
- 17 May 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
van Baar MJB, Bjornstad P, Touw DJ, Joles JA, Krebber MM, Cherney DZI, van Raalte DH, Muskiet MHA. Renal functional reserve predicts GFR response to empagliflozin in RENALIS and RACELINES clinical trials. Nephrol Dial Transplant. 2026 Jul 31;41(8):1520-1528. doi: 10.1093/ndt/gfag025.
PubMed 41665872Muskiet MHA, Tonneijck L, Smits MM, Kramer MHH, Ouwens DM, Hartmann B, Holst JJ, Touw DJ, Danser AHJ, Joles JA, van Raalte DH. Effects of DPP-4 Inhibitor Linagliptin Versus Sulfonylurea Glimepiride as Add-on to Metformin on Renal Physiology in Overweight Patients With Type 2 Diabetes (RENALIS): A Randomized, Double-Blind Trial. Diabetes Care. 2020 Nov;43(11):2889-2893. doi: 10.2337/dc20-0902. Epub 2020 Sep 8.
PubMed 32900785
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4, Monocenter, Randomized, Double-blind, Comparator-controlled, Parallel-group, Mechanistic Intervention Trial to Assess the Effect of 8-week Treatment With the Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Linagliptin Versus the Sulfonylurea (SU) Derivative Glimepiride on Renal Physiology and Biomarkers in Metformin-treated Patients With Type 2 Diabetes Mellitus (T2DM)
- ClinicalTrials.gov ID
- NCT02106104
- Acronym / sponsor ID
- RENALIS / DC2013RENALIS
- Conditions
- Type 2 Diabetes
- Keywords
- Type 2 diabetes mellitus, Diabetic kidney disease, Diabetic nephropathy, Renoprotection, DPP-4 inhibitors, Linagliptin, SU derivatives, Glimepiride
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 8 Apr 2014 (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 DPP-4 inhibitor linagliptin on the renal system in patients with type 2 diabetes mellitus.
Detailed description
Based on preclinical and small-sized studies in non-diabetic individuals, incretin-based therapies, i.e. glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i), may hold promise in preventing the onset and progression of diabetic kidney disease. However, the potential renoprotective effects of these agents, that are believed to be effectuated "beyond glucose control", have not been sufficiently detailed in human diabetes.
Therefore, the present study aims to explore the mechanistic and clinical effects of DPP-4i on fasting and postprandial renal physiology and biomarkers in patients with type 2 diabetes.
Forty-eight patients with type 2 diabetes will undergo an eight week intervention with linagliptin or glimepiride in order to assess changes in the outcome parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linagliptin 5 mg QD (N=24) | Experimental | Drug: Linagliptin 5 mg QD (N=24)Linagliptin 5 mg will be taken orally, once daily for 8 weeks |
| Glimepiride 1 mg QD (N=24) | Active comparator | Drug: Glimepiride 1 mg QD (N=24)Glimepiride 1 mg will be taken orally, once daily for 8 weeks |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with type 2 diabetes (HbA1c: 6.5-9.0% DCCT or 48-75 mmol/mol IFCC)
- Metformin monotherapy; using a stable dose for at least 3 months prior to inclusion
- Both genders (females must be post-menopausal)
- Caucasian
- Age: 35-75 years
Key exclusion criteria (15 listed)
- Current / chronic use of the following medication: thiazolidinediones, insulin, glucocorticoids, immune suppressants, antimicrobial agents or chemotherapeutics. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study
- Chronic use of NSAIDs will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications. However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing
- Pregnancy
- Frequent occurrence of (confirmed) hypoglycemia (plasma glucose <3.9 mmol/L)
- Estimated Glomerular Filtration Rate < 60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
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 |
|---|---|---|
| Linagliptin 5 mg QD (N=24)Also: TrajentaLinagliptin 5 mg will be taken orally, once daily for 8 weeks | Drug | Linagliptin 5 mg QD (N=24) |
| Glimepiride 1 mg QD (N=24)Also: AmarylGlimepiride 1 mg will be taken orally, once daily for 8 weeks | Drug | Glimepiride 1 mg QD (N=24) |
Primary outcome
Changes from baseline following 8-week treatment with linagliptin vs glimepiride on fasting and postprandial renal hemodynamics, measured as GFR / ERPF (determined by inulin/para-aminohippuric-acid clearance)
Time frame: 8 weeks
3 secondary outcomes
Renal tubular function
Time frame: 8 weeks
Renal damage, measured by urine biomarkers
Time frame: 8 weeks
Blood Pressure and Heart Rate
Time frame: 8 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 17 May 2016.
- Derived from this study: PubMed 41665872van Baar MJB, Bjornstad P, Touw DJ, Joles JA, Krebber MM, Cherney DZI, van Raalte DH, Muskiet MHA. Renal functional reserve predicts GFR response to empagliflozin in RENALIS and RACELINES clinical trials. Nephrol Dial Transplant. 2026 Jul 31;41(8):1520-1528. doi: 10.1093/ndt/gfag025.
- Derived from this study: PubMed 32900785Muskiet MHA, Tonneijck L, Smits MM, Kramer MHH, Ouwens DM, Hartmann B, Holst JJ, Touw DJ, Danser AHJ, Joles JA, van Raalte DH. Effects of DPP-4 Inhibitor Linagliptin Versus Sulfonylurea Glimepiride as Add-on to Metformin on Renal Physiology in Overweight Patients With Type 2 Diabetes (RENALIS): A Randomized, Double-Blind Trial. Diabetes Care. 2020 Nov;43(11):2889-2893. doi: 10.2337/dc20-0902. Epub 2020 Sep 8.
- Individual participant dataSharing planned: Undecided
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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.
Mark 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 Linagliptin 5 mg QD (N=24) and Glimepiride 1 mg QD (N=24) 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 7 inclusion and 15 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 17 May 2016. 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. 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 8-week treatment with linagliptin vs glimepiride on fasting and postprandial renal hemodynamics, measured as GFR / ERPF (determined by inulin/para-aminohippuric-acid clearance) (time frame: 8 weeks). 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 NCT02106104, which also lists 2 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 17 May 2016.