Effects of Linagliptin on Endothelial- , Renal-, and Retinal Function in Patients With Hypertension and Albuminuria
Condition: Arterial Hypertension; Albuminuria
MeSH terms: Albuminuria; Hypertension
Study type: Interventional
Phase: Phase 3

Summary: 
      A recent study with the DPP-IV inhibitor Linagliptin showed an improvement in the urinary
      albumin creatinine ratio in patients with diabetic nephropathy. Gutzwiller et. Al. have shown
      that GLP-1 increases renal Na secretion and inhibits renal H secretion, further indicating
      some direct renal effects of GLP-1.

      Therefore, it seems likely that treatment with the DPP-IV inhibitor Linagliptin evolves
      several beneficial effects on microvascular and endothelial function beyond glucose control
      which most probably have an impact on the progression of renal and retinal microvascular
      disease.

      The objective of this trial is to investigate the effect of Linagliptin in comparison to
      placebo on the UACR in patients with high blood pressure and an increased albumin excretion.
      Numerous, equivalent endothelial, renal, and retinal parameters serve as objectives of the
      study. All study parameters will be handled in an exploratory sense for the generation of
      models to further discuss the role of DPP-IV inhibition on renal and retinal physiology.
    

Detailed description: 
      Renal tissue damage and an increase in the albumin excretion rate is a strong predictor for
      the development and progression of endothelial dysfunction and the development of
      microvascular and/or macrovascular complications. Increased blood pressure as well as
      increased glucose levels were found to impair renal- and retinal function, and a close
      association in the incidence and progression rate of retinopathy and nephropathy could be
      observed. Endothelial dysfunction and alterations in microvascular blood flow are early
      pathogenetic features in the development of renal and retinal tissue damage as found in
      patients with arterial hypertension and / or diabetes mellitus. A couple of studies have
      shown that urinary albumin excretion is associated with morphological and functional
      alterations in retinal microvascular blood flow. In patients with arterial hypertension blood
      pressure lowering treatment were shown to decrease the albumin excretion rate and to improve
      endothelial function of the retinal vasculature.

      Recently DPP-IV Inhibitors have been introduced in the treatment of type 2 diabetes mellitus.
      Beside the metabolic effects of this drug class, several pleiotropic effects beyond metabolic
      control were documented in numerous studies, and are the topic of ongoing clinical research.
      Treatment with DPP-IV inhibitors was found to improve myocardial and endothelial function, to
      improve blood lipids, to lower blood pressure and to improve markers of renal function. GLP-1
      receptors in vessels, kidney and the heart might account for those glucose independent
      effects of GLP-1. However, it is also conceivable that DPP-IV inhibition might exert vascular
      effects independent from GLP-1. In vitro studies demonstrated that DPP-IV is expressed in
      endothelial cells, and the inhibition of DPP-IV reduced the microvascular tone through direct
      mediation of the nitric oxide system. Therefore, it seems conceivable that the glucose
      independent effects of DPP-IV inhibition might be mediated through GLP-1 receptor signaling
      and /or direct inhibition of the enzyme DPP-IV in vascular, renal, or retinal cells.

      A recent study with the DPP-IV inhibitor Linagliptin showed an improvement in the urinary
      albumin creatinine ratio in patients with diabetic nephropathy. Gutzwiller et. Al. have shown
      that GLP-1 increases renal Na secretion and inhibits renal H secretion, further indicating
      some direct renal effects of GLP-1.

      Therefore, it seems likely that treatment with the DPP-IV inhibitor Linagliptin evolves
      several beneficial effects on microvascular and endothelial function beyond glucose control
      which most probably have an impact on the progression of renal and retinal microvascular
      disease.

      The objective of this trial is to investigate the effect of Linagliptin in comparison to
      placebo on the UACR in patients with high blood pressure and an increased albumin excretion.
      Numerous, equivalent endothelial, renal, and retinal parameters serve as objectives of the
      study. All study parameters will be handled in an exploratory sense for the generation of
      models to further discuss the role of DPP-IV inhibition on renal and retinal physiology.
    

Intervention name(s): Linagliptin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Intake of tablets containing 5 mg Linagliptin, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks; Intake of Placebo, administered once daily as add on to pre-existing antihypertensive treatment for 6 weeks
Other intervention name(s): Trajenta
Intervention MeSH terms: Linagliptin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)