Long Term Effects of DPP-IV Inhibitor Treatment in Patients With Type 2 Diabetes
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

Summary: 
      We wish to evaluate the effect of long term treatment with a DPP-IV inhibitor on the function
      of the incretin hormones

      Hypothesis We hypothesize that that a gradual improvement in metabolic control induced by
      DPP-IV inhibitor (Januvia®) treatment significantly ameliorates the impaired secretion and
      potency of GLP-1 and leads to a restoration of the lost action of GIP.
    

Detailed description: 
      Background The incretin effect, primarily mediated by the peptide hormones GIP and GLP-1, is
      known to be impaired in patients with type 2 diabetes, and characterised by reduced GLP-1
      secretion and potency and a lack of responsiveness to the insulinotropic effect of GIP. The
      cause of this defect remains unknown, but exogenous administration of GLP-1 has shown
      promising results in attempts to restore the incretin effect. Due to rapid degradation of
      both incretin hormones by the enzyme dipeptidyl-peptidase IV (DPP-IV), treatment strategies
      now focus on GLP-1 analogues and prevention of hormone degradation through DPP-IV inhibition.

      Hypothesis We hypothesize that that a gradual improvement in metabolic control induced by
      DPP-IV inhibitor (Januvia®) treatment significantly ameliorates the impaired secretion and
      potency of GLP-1 and leads to a restoration of the lost action of GIP.

      Objective To assess the effect of three months treatment with Januvia®, administered as
      tablets once daily, on metabolic control in metformin treated patients with type 2 diabetes,
      measured as increases in incretin hormones and insulin secretion.

      Efficacy end points Primary efficacy end point in trial part one is the relative increase in
      meal-induced total GLP-1 secretion after one and twelve weeks of Januvia® treatment.

      Primary efficacy end point in part two is restoration of the insulinotropic effect of GIP,
      measured as the relative increase in GIP induced amplification of the late phase insulin
      secretion (AUC) response to glucose after 12 weeks of Januvia® treatment.

      Secondary objectives are examination of GLP-2, somatostatin, glucagon, peptide-YY and two
      glycaemic control parameters (HbA1c and fasting plasma glucose)

      Design This is a single centre, randomized, double blinded, placebo controlled trial. The
      trial consists of two parts, each consisting of three months of inhibitor treatment. In each
      part, 24 patients, recruited from the Diabetes Outpatient Clinic of Gentofte University
      Hospital, will be randomized to a treatment supplement of either Januvia® or placebo.

      Procedures During the trial, patients will be tested with well established procedures. In
      part one, patients will undergo a standardized meal test and two β-cell secretory capacity
      tests. In part two, patients will undergo standardized hyperglycaemic GIP, GLP-1 and saline
      clamps.

      Safety The trial has a short time span of only three months. With more than ten visits during
      this time and regular blood sampling, the patients are well monitored.
    

Intervention name(s): Januvia; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 200 mg t.i.d; Placebo
Other intervention name(s): Sitagliptin
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: GLP-1; GIP; Incretin hormones; DPP-IV inhibitor; Hyperglycaemic clamp; Meal test