Off taRget Effects of Linagliptin monothErapy on Arterial Stiffness in Early Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

Summary: 
      Diabetes is associated with an increased risk for developing premature macrovascular
      complications. The process of irreversible subclinical damage to the vasculature already
      starts during its preceding stages. Dipeptidyl peptidase (DPP)-4 inhibitors have been shown
      to attenuate vascular damage in preclinical studies. Off-target effects on adipose tissue
      inflammation, liver steatosis and atherosclerotic plaques have been extensively documented in
      animal studies.

      Based on these considerations the investigators hypothesize that early therapy with the DPP4
      inhibitor linagliptin in subjects with treatment naive type 2 diabetes will lead to
      beneficial effects on arterial stiffness as measured by pulse wave velocity.
    

Detailed description: 
      Patients with type 2 diabetes mellitus (T2DM) are at increased risk for developing premature
      macrovascular complications. The process of irreversible subclinical damage to the
      vasculature already starts during its preceding stages. At diagnosis, patients with T2DM
      already have evidence of subclinical vascular damage. Recent trials have shown no benefit of
      glucose lowering therapy when started later in the course of the disease, implicating that
      early interventions could be more effective in preventing macrovascular complications.
      Dipeptidyl peptidase (DPP)-4 inhibitors are oral antidiabetic drugs that increase the action
      of the naturally gut hormone glucagon-like peptide-1 (GLP-1), leading to improvement of
      postprandial insulin secretion, without hypoglycaemia or weight gain. DPP4 inhibitors improve
      beta-cell function and insulin resistance. More importantly, off-target effects on adipose
      tissue inflammation, liver steatosis and atherosclerotic plaques have been extensively
      documented in animal studies. Furthermore, DDP4 inhibitors improve the cardiovascular risk
      profile in small clinical studies. Based on these considerations the investigators
      hypothesize that early therapy with the DPP4 inhibitor linagliptin in subjects with type 2
      diabetes will lead to beneficial effects on arterial stiffness, blood pressure and
      inflammatory markers independent of its effects on glycemic control.
    

Intervention name(s): Linagliptin; placebo
Intervention type(s): Drug; Drug
Intervention description(s): one tablet linagliptin 5 mg/day for 26 weeks; one tablet matching placebo/day for 26 weeks
Other intervention name(s): Trajenta; DPP-4 inhibitor
Intervention MeSH terms: Linagliptin; Dipeptidyl-Peptidase IV Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Diabetes; Pulse Wave Velocity; Dipeptidyl peptidase (DPP)-4 inhibitors; Linagliptin; Arterial Stiffness; Subclinical arterial inflammation