Comparing the Renal Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas
Condition: Type 2 Diabetes Mellitus; Proteinuria
MeSH terms: Proteinuria; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): Dipeptidyl Peptidase 4 Inhibitor; Sulfonylurea
Intervention type(s): Drug; Drug
Intervention description(s): Vildagliptin 50 milligrams twice daily in addition to metformin 1000 milligrams once daily; Glimepiride 2 milligrams twice daily in addition to metformin 1000 milligrams once daily
Other intervention name(s): DPP-4 inhibitor; SU
Intervention MeSH terms: Dipeptidyl-Peptidase IV Inhibitors
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 2 diabetes mellitus; dipeptidyl peptidase 4 inhibitors; sulfonylureas; proteinuria