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

Sponsor

Changhua Christian Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03983551

Collaborator

(none)

101

Enrollment

Arms

Actual Duration (Months)

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Proteinuria	Drug: Dipeptidyl Peptidase 4 Inhibitor Drug: Sulfonylurea	Phase 4

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

Study Type:

Interventional

Actual Enrollment :

101 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Comparing the Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas on Urinary Albumin Excretion in People With Type 2 Diabetes Mellitus

Actual Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Feb 10, 2018

Actual Study Completion Date :

Feb 28, 2018

Arms and Interventions

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

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:

Outcome Measures

Primary Outcome Measures

Change in urinary albumin-to-creatinine ratio [24 weeks]
Change in urinary albumin-to-creatinine ratio after pharmacologic treatment

Secondary Outcome Measures

Change in serum glycated hemoglobin A1c [24 weeks]
Change in serum glycated hemoglobin A1c after pharmacologic treatment
Change in body weight [24 weeks]
Change in body weight after pharmacologic treatment
Change in serum creatinine [24 weeks]
Change in serum creatinine after pharmacologic treatment
Change in systolic blood pressure [24 weeks]
Change in systolic blood pressure after pharmacologic treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 95 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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