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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03983551
• Other study ID #: 190512
• Status: Completed
• Phase: Phase 4
• Start date: March 1, 2016
• Est. completion date: February 28, 2018

Study information

• Verified date: June 2019
• Source: Changhua Christian Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: February 28, 2018
• Est. primary completion date: February 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 95 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Proteinuria
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Dipeptidyl Peptidase 4 Inhibitor
Vildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily
• Sulfonylurea
Glimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Changhua Christian Hospital

References & Publications (8)

Davidson 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. Review. — View Citation

Introduction: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S1-S2. doi: 10.2337/dc18-Sint01. — View Citation

Kim 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. Review. — View Citation

Makino 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. Review. — View Citation

Mishra 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. — View Citation

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. Review. — View Citation

Sola D, Rossi L, Schianca GP, Maffioli P, Bigliocca M, Mella R, Corlianò 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. — View Citation

Stanton 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in urinary albumin-to-creatinine ratio	Change in urinary albumin-to-creatinine ratio after pharmacologic treatment	24 weeks
Secondary	Change in serum glycated hemoglobin A1c	Change in serum glycated hemoglobin A1c after pharmacologic treatment	24 weeks
Secondary	Change in body weight	Change in body weight after pharmacologic treatment	24 weeks
Secondary	Change in serum creatinine	Change in serum creatinine after pharmacologic treatment	24 weeks
Secondary	Change in systolic blood pressure	Change in systolic blood pressure after pharmacologic treatment	24 weeks