The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion

University Health Network, Toronto

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes

Treatments: Drug: Sitaglitpin; Other: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02406443

14-8616

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Individuals of 18-70 years of age,
• with Type 2 Diabetes,
• with an HbA1c (6.5%-9%),
• and with a systolic blood pressure (120-160 mmHg).

Exclusion criteria

• Individuals with:

  1. Type 1 Diabetes,
  2. eGFR <50mL/min/1.73m,
  3. pregnancy or breast feeding,
  4. significant cardiac, pulmonary or liver disease,
  5. prior history of pancreatitis, medullary thyroid cancer, multiple endocrine neoplasia syndromes,
  6. SBP >161 mmHg, 7) DBP >100 mmHg,
  7. alcohol or substance abuse,
  8. states of secondary hypertension.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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36 participants in 2 patient groups, including a placebo group

Experimental arm

Experimental group

Description:

sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days

Treatment:

Drug: Sitaglitpin

Placebo arm

Placebo Comparator group

Description:

placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days

Treatment:

Other: Placebo