Comparing the Renal Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas

June 12, 2019 updated by: Po-Chung Cheng, Changhua Christian Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients exceeding 20 years of age
  • Patients with newly diagnosed type 2 diabetes mellitus
  • Patients who have yet to receive antidiabetic medications

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dipeptidyl peptidase 4 inhibitors
Vildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily
Drug: Dipeptidyl Peptidase 4 Inhibitor
Vildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily
Other Names:
  • DPP-4 inhibitor
Active Comparator: Sulfonylureas
Glimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily
Drug: Sulfonylurea
Glimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily
Other Names:
  • SU

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in urinary albumin-to-creatinine ratio
Time Frame: 24 weeks
Change in urinary albumin-to-creatinine ratio after pharmacologic treatment
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum glycated hemoglobin A1c
Time Frame: 24 weeks
Change in serum glycated hemoglobin A1c after pharmacologic treatment
24 weeks
Change in body weight
Time Frame: 24 weeks
Change in body weight after pharmacologic treatment
24 weeks
Change in serum creatinine
Time Frame: 24 weeks
Change in serum creatinine after pharmacologic treatment
24 weeks
Change in systolic blood pressure
Time Frame: 24 weeks
Change in systolic blood pressure after pharmacologic treatment
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Changhua Christian Hospital

Investigators

  • Study Director: Shih Te Tu, MD, Changhua Christian Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

February 10, 2018

Study Completion (Actual)

February 28, 2018

Study Registration Dates

First Submitted

June 11, 2019

First Submitted That Met QC Criteria

June 11, 2019

First Posted (Actual)

June 12, 2019

Study Record Updates

Last Update Posted (Actual)

June 14, 2019

Last Update Submitted That Met QC Criteria

June 12, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 190512

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All individual participant data that underlie results in a publication.

IPD Sharing Time Frame

Starting immediately after publication.

IPD Sharing Access Criteria

Available to any interested researcher.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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