The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      Background: Dedicated renal hemodynamic and renal function studies are lacking for DPP-4
      inhibitors in patients with Type 2 diabetes; accordingly little is known regarding the
      mechanisms mediating the renal effects of DPP-4 inhibitors in humans.

      Objectives: To evaluate the effect of DPP-4 inhibition acutely (single dose) and following
      short-term therapy (28 days) on renal sodium handling and renal hemodynamics and function in
      patients with type 2 diabetes and systolic hypertension.

      Design: double-blind, randomized, placebo-controlled trial, Phase IV.

      Patient population: 32 patients with Type 2 diabetes, HbA1c (6.5%-9%), with systolic blood
      pressure ranging from 120-160 mmHg.

      Intervention: subjects will be randomized (1:1) to either sitagliptin (100 mg daily) or to
      placebo (1 tablet daily) for 28 days.

      Endpoints: Fractional excretion of sodium, renal function, and renal hemodynamics.
    

Detailed description: 
      Background: DPP-4 inhibition improves glycemic control, modestly reduces blood pressure and
      may also reduce albuminuria in patients with Type 2 diabetes; effects which occur without
      significantly modifying heart rate or body weight. While preclinical studies have
      demonstrated that DPP-4 inhibition acutely increases urinary sodium excretion in addition to
      other favorable renal effects (anti-inflammatory, anti-proteinuric), few studies have
      examined the renal effects of DPP-4 inhibition either acutely or following short-term therapy
      in humans with type 2 diabetes. Considering the world-wide prevalence of Type 2 diabetes and
      the increasing use of DPP-4 inhibitors amongst patients, it is important to ascertain
      potential non-glycemic effects of DPP-4 inhibitors including those within the kidney.

      Study Objectives: To determine effect(s) of DPP-4 inhibition on tubular sodium handling,
      renal hemodynamics, and renal function.

      Study Design: double-blind, randomized, placebo-controlled trial, Phase IV.

      Study Patients: 32 patients with Type 2 Diabetes and Systolic Hypertension (SBP 120-160
      mmHg).

      Endpoints: Fractional excretion of sodium, renal function (measured GFR), renal hemodynamics
      (effective renal plasma flow, filtration fraction, renal blood flow, renal vascular
      resistance), systemic hemodynamics (non-invasive cardiac monitoring), plasma neurohormones,
      urinary vasoactive mediators, markers of free radical stress.
    

Intervention name(s): Sitaglitpin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days; Oral tablet (no medicinal ingredients) administered once daily for 28 days
Other intervention name(s): Januvia
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Type 2 Diabetes, DPP-4 inhibitors, renal sodium excretion