Type 2 Diabetes MellitusPhase 4NCT03983551
Comparing the Renal Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas
A Phase 4 study testing Dipeptidyl Peptidase 4 Inhibitor and Sulfonylurea in people with Type 2 Diabetes Mellitus and Proteinuria, run by Changhua Christian Hospital.
Trial summary
Dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas have been extensively used in the treatment of type 2 diabetes mellitus (T2DM). Although both medications effectively lower plasma glucose levels, differences may exist in their pharmacokinetics and effect on the kidney. Read more about this study
- Who is it for?
- Ages 20 to 95 years
- Conditions the study is for
- Type 2 Diabetes Mellitus, Proteinuria
- What is being tested?
- Dipeptidyl Peptidase 4 Inhibitor and Sulfonylurea
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2016to 28 Feb 2018
- 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 20 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients exceeding 20 years of age
- Patients with newly diagnosed type 2 diabetes mellitus
- Patients who have yet to receive antidiabetic medications
Who cannot join
- Patients with non-diabetic kidney disease
- Patients with congenital kidney abnormalities
- Patients with end stage renal disease.
- Patients who have received angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker
About this study
Official title: Comparing the Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas on Urinary Albumin Excretion in People With Type 2 Diabetes Mellitus
Dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas have been extensively used in the treatment of type 2 diabetes mellitus (T2DM). Although both medications effectively lower plasma glucose levels, differences may exist in their pharmacokinetics and effect on the kidney. In the context of diabetic kidney disease, DPP-4 inhibitors may confer renal protection through several putative mechanisms. In contrast, sulfonylureas are associated with weight gain and cardiac dysfunction, which may adversely influence kidney function.
The investigators hypothesize that DPP-4 inhibitors and sulfonylureas may have a different effect on the diabetic kidney. This study compares the effect of DPP-4 inhibitors and sulfonylureas on urinary albumin excretion in patients with newly diagnosed T2DM.
Read the detailed description
Diabetic kidney disease (DKD) occurs in a considerable number of individuals with type 2 diabetes mellitus (T2DM). DKD leads to substantial morbidity and reduces the quality of life in afflicted patients. Chronic hyperglycemia induces proapoptotic signaling pathways in mesangial cells, leading to microvascular injury in the diabetic kidney. Clinical interventions targeting plasma glucose, body weight, and blood pressure have been shown to attenuate the progression of DKD.
Dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas have been extensively used in the treatment of T2DM. Although both medications effectively lower plasma glucose levels, differences may exist in their pharmacokinetics and effect on the kidney. In the context of DKD, DPP-4 inhibitors may confer renal protection through several putative mechanisms. However, whether such renal protection involves the glucose lowering efficacy of DPP-4 inhibitors or additional mechanisms remains controversial. In contrast, currently there is inadequate information concerning the effect of sulfonylureas on the development of DKD. If the glucose lowering effect of DPP-4 inhibitors is a major determinant of renal protection, then sulfonylureas may theoretically offer similar benefit by maintaining euglycemia. However, sulfonylureas are associated with weight gain and cardiac dysfunction, which may adversely influence kidney function.
Given that DPP-4 inhibitors and sulfonylureas have different effect on physiologic parameters including body weight and blood pressure, the investigators hypothesize that these medications may have different effects on the diabetic kidney. This study compares the effect of DPP-4 inhibitors and sulfonylureas on urinary albumin excretion in patients with newly diagnosed T2DM.
In this study, patients with newly diagnosed T2DM are screened for eligibility. All participants receive 1000 mg of metformin therapy at the beginning of the study. Subsequently, patients are assigned to receive either the DPP-4 inhibitor Vildagliptin 50 mg twice daily or the sulfonylurea Glimepiride 2 mg twice daily. Treatment allocation is made by a committee of endocrinologists to match participants in the treatment groups by age, body weight, serum glycated hemoglobin (HbA1c), urinary albumin-to-creatinine ratio (ACR), and serum creatinine.
At the initial clinic visit, participants receive blood tests for serum HbA1c, serum creatinine, serum alanine transferase, and plasma lipid profile after a 12-hour fast. Urine samples will be collected in the morning after a 12-hour fast, and urinary ACR is measured by the turbidimetric method. Laboratory tests for these clinical variables are repeated after 24 weeks of pharmacologic treatment. Participants who loss follow up or withdraw from the study will be assessed by an intention to treat analysis. The change in urinary ACR is defined as the primary outcome measure, whereas changes in serum HbA1c, serum creatinine, body weight, and systolic blood pressure are considered secondary outcome measures.
- Conditions
- Type 2 Diabetes Mellitus, Proteinuria
- Being tested
- Dipeptidyl Peptidase 4 Inhibitor, Sulfonylurea
- Keywords
- Type 2 diabetes mellitus, dipeptidyl peptidase 4 inhibitors, sulfonylureas, proteinuria
- Medical subject headings
- Diabetes Mellitus, Type 2, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dipeptidyl Peptidase 4 InhibitorDrug
Also called DPP-4 inhibitor
Vildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily
SulfonylureaDrug
Also called SU
Glimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily
| Study group | Role | What they receive |
|---|---|---|
| Dipeptidyl peptidase 4 inhibitors | Experimental | Vildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily Receives: Drug: Dipeptidyl Peptidase 4 Inhibitor |
| Sulfonylureas | Active comparator | Glimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily Receives: Drug: Sulfonylurea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in urinary albumin-to-creatinine ratio
Change in urinary albumin-to-creatinine ratio after pharmacologic treatment
Measured: 24 weeks
Secondary outcomes (4)
Change in serum glycated hemoglobin A1c
Change in serum glycated hemoglobin A1c after pharmacologic treatment
Measured: 24 weeks
Change in body weight
Change in body weight after pharmacologic treatment
Measured: 24 weeks
Change in serum creatinine
Change in serum creatinine after pharmacologic treatment
Measured: 24 weeks
Change in systolic blood pressure
Change in systolic blood pressure after pharmacologic treatment
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2019
- Study start1 Mar 2016
- Primary completion10 Feb 2018
- Study completion28 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Changhua Christian Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Po-Chung Cheng, Changhua Christian Hospital
- Investigators
- Shih Te Tu, MD, Study director, Changhua Christian Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03983551
- Sponsor's protocol ID
- 190512
- Status last verified
- Jun 2019
- First submitted
- 11 Jun 2019
- Last updated
- 14 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data that underlie results in a publication.
Publications
Park CW. Diabetic kidney disease: from epidemiology to clinical perspectives. Diabetes Metab J. 2014 Aug;38(4):252-60. doi: 10.4093/dmj.2014.38.4.252.
PubMed 25215271Stanton RC. Clinical challenges in diagnosis and management of diabetic kidney disease. Am J Kidney Dis. 2014 Feb;63(2 Suppl 2):S3-21. doi: 10.1053/j.ajkd.2013.10.050.
PubMed 24461728Mishra R, Emancipator SN, Kern T, Simonson MS. High glucose evokes an intrinsic proapoptotic signaling pathway in mesangial cells. Kidney Int. 2005 Jan;67(1):82-93. doi: 10.1111/j.1523-1755.2005.00058.x.
PubMed 15610231Kim MK. Treatment of diabetic kidney disease: current and future targets. Korean J Intern Med. 2017 Jul;32(4):622-630. doi: 10.3904/kjim.2016.219. Epub 2017 Jun 30.
PubMed 28704915Introduction: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S1-S2. doi: 10.2337/dc18-Sint01. No abstract available.
PubMed 29222369Davidson JA. The placement of DPP-4 inhibitors in clinical practice recommendations for the treatment of type 2 diabetes. Endocr Pract. 2013 Nov-Dec;19(6):1050-61. doi: 10.4158/EP12303.RA.
PubMed 24126227Makino Y, Fujita Y, Haneda M. Dipeptidyl peptidase-4 inhibitors in progressive kidney disease. Curr Opin Nephrol Hypertens. 2015 Jan;24(1):67-73. doi: 10.1097/MNH.0000000000000080.
PubMed 25415611Sola D, Rossi L, Schianca GP, Maffioli P, Bigliocca M, Mella R, Corliano F, Fra GP, Bartoli E, Derosa G. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015 Aug 12;11(4):840-8. doi: 10.5114/aoms.2015.53304. Epub 2015 Aug 11.
PubMed 26322096
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing the Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas on Urinary Albumin Excretion in People With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT03983551
- Acronym / sponsor ID
- 190512
- Conditions
- Type 2 Diabetes Mellitus, Proteinuria
- Keywords
- Type 2 diabetes mellitus, dipeptidyl peptidase 4 inhibitors, sulfonylureas, proteinuria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Changhua Christian HospitalUniversity, hospital or other
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 10 Feb 2018 (actual)
- Study completion
- 28 Feb 2018 (actual)
- First posted
- 12 Jun 2019 (actual)
- 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.
Dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas have been extensively used in the treatment of type 2 diabetes mellitus (T2DM). Although both medications effectively lower plasma glucose levels, differences may exist in their pharmacokinetics and effect on the kidney. In the context of diabetic kidney disease, DPP-4 inhibitors may confer renal protection through several putative mechanisms. In contrast, sulfonylureas are associated with weight gain and cardiac dysfunction, which may adversely influence kidney function.
The investigators hypothesize that DPP-4 inhibitors and sulfonylureas may have a different effect on the diabetic kidney. This study compares the effect of DPP-4 inhibitors and sulfonylureas on urinary albumin excretion in patients with newly diagnosed T2DM.
Detailed description
Diabetic kidney disease (DKD) occurs in a considerable number of individuals with type 2 diabetes mellitus (T2DM). DKD leads to substantial morbidity and reduces the quality of life in afflicted patients. Chronic hyperglycemia induces proapoptotic signaling pathways in mesangial cells, leading to microvascular injury in the diabetic kidney. Clinical interventions targeting plasma glucose, body weight, and blood pressure have been shown to attenuate the progression of DKD.
Dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas have been extensively used in the treatment of T2DM. Although both medications effectively lower plasma glucose levels, differences may exist in their pharmacokinetics and effect on the kidney. In the context of DKD, DPP-4 inhibitors may confer renal protection through several putative mechanisms. However, whether such renal protection involves the glucose lowering efficacy of DPP-4 inhibitors or additional mechanisms remains controversial. In contrast, currently there is inadequate information concerning the effect of sulfonylureas on the development of DKD. If the glucose lowering effect of DPP-4 inhibitors is a major determinant of renal protection, then sulfonylureas may theoretically offer similar benefit by maintaining euglycemia. However, sulfonylureas are associated with weight gain and cardiac dysfunction, which may adversely influence kidney function.
Given that DPP-4 inhibitors and sulfonylureas have different effect on physiologic parameters including body weight and blood pressure, the investigators hypothesize that these medications may have different effects on the diabetic kidney. This study compares the effect of DPP-4 inhibitors and sulfonylureas on urinary albumin excretion in patients with newly diagnosed T2DM.
In this study, patients with newly diagnosed T2DM are screened for eligibility. All participants receive 1000 mg of metformin therapy at the beginning of the study. Subsequently, patients are assigned to receive either the DPP-4 inhibitor Vildagliptin 50 mg twice daily or the sulfonylurea Glimepiride 2 mg twice daily. Treatment allocation is made by a committee of endocrinologists to match participants in the treatment groups by age, body weight, serum glycated hemoglobin (HbA1c), urinary albumin-to-creatinine ratio (ACR), and serum creatinine.
At the initial clinic visit, participants receive blood tests for serum HbA1c, serum creatinine, serum alanine transferase, and plasma lipid profile after a 12-hour fast. Urine samples will be collected in the morning after a 12-hour fast, and urinary ACR is measured by the turbidimetric method. Laboratory tests for these clinical variables are repeated after 24 weeks of pharmacologic treatment. Participants who loss follow up or withdraw from the study will be assessed by an intention to treat analysis. The change in urinary ACR is defined as the primary outcome measure, whereas changes in serum HbA1c, serum creatinine, body weight, and systolic blood pressure are considered secondary outcome measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dipeptidyl peptidase 4 inhibitors | Experimental | Drug: Dipeptidyl Peptidase 4 InhibitorVildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily |
| Sulfonylureas | Active comparator | Drug: SulfonylureaGlimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily |
Who may qualify
- Ages
- 20 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients exceeding 20 years of age
- Patients with newly diagnosed type 2 diabetes mellitus
- Patients who have yet to receive antidiabetic medications
Key exclusion criteria (4 listed)
- Patients with non-diabetic kidney disease
- Patients with congenital kidney abnormalities
- Patients with end stage renal disease.
- Patients who have received angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker
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 |
|---|---|---|
| Dipeptidyl Peptidase 4 InhibitorAlso: DPP-4 inhibitorVildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily | Drug | Dipeptidyl peptidase 4 inhibitors |
| SulfonylureaAlso: SUGlimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily | Drug | Sulfonylureas |
Primary outcome
Change in urinary albumin-to-creatinine ratio
Time frame: 24 weeks
Change in urinary albumin-to-creatinine ratio after pharmacologic treatment
4 secondary outcomes
Change in serum glycated hemoglobin A1c
Time frame: 24 weeks
Change in body weight
Time frame: 24 weeks
Change in serum creatinine
Time frame: 24 weeks
Change in systolic blood pressure
Time frame: 24 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 14 Jun 2019.
- Background: PubMed 25215271Park CW. Diabetic kidney disease: from epidemiology to clinical perspectives. Diabetes Metab J. 2014 Aug;38(4):252-60. doi: 10.4093/dmj.2014.38.4.252.
- Background: PubMed 24461728Stanton RC. Clinical challenges in diagnosis and management of diabetic kidney disease. Am J Kidney Dis. 2014 Feb;63(2 Suppl 2):S3-21. doi: 10.1053/j.ajkd.2013.10.050.
- Background: PubMed 15610231Mishra R, Emancipator SN, Kern T, Simonson MS. High glucose evokes an intrinsic proapoptotic signaling pathway in mesangial cells. Kidney Int. 2005 Jan;67(1):82-93. doi: 10.1111/j.1523-1755.2005.00058.x.
- Background: PubMed 28704915Kim MK. Treatment of diabetic kidney disease: current and future targets. Korean J Intern Med. 2017 Jul;32(4):622-630. doi: 10.3904/kjim.2016.219. Epub 2017 Jun 30.
- Background: PubMed 29222369Introduction: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S1-S2. doi: 10.2337/dc18-Sint01. No abstract available.
- Background: PubMed 24126227Davidson JA. The placement of DPP-4 inhibitors in clinical practice recommendations for the treatment of type 2 diabetes. Endocr Pract. 2013 Nov-Dec;19(6):1050-61. doi: 10.4158/EP12303.RA.
- Background: PubMed 25415611Makino Y, Fujita Y, Haneda M. Dipeptidyl peptidase-4 inhibitors in progressive kidney disease. Curr Opin Nephrol Hypertens. 2015 Jan;24(1):67-73. doi: 10.1097/MNH.0000000000000080.
- Background: PubMed 26322096Sola D, Rossi L, Schianca GP, Maffioli P, Bigliocca M, Mella R, Corliano F, Fra GP, Bartoli E, Derosa G. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015 Aug 12;11(4):840-8. doi: 10.5114/aoms.2015.53304. Epub 2015 Aug 11.
- Individual participant dataSharing planned: Yes. All individual participant data that underlie results in a publication.
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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.
Shih Te Tu, MD study director
Changhua Christian Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dipeptidyl Peptidase 4 Inhibitor and Sulfonylurea in people with Type 2 Diabetes Mellitus and Proteinuria, run by Changhua Christian Hospital.
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 3 inclusion and 4 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 14 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Change in urinary albumin-to-creatinine ratio (time frame: 24 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 NCT03983551, which also lists 8 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 14 Jun 2019.