The Impact of Sitagliptin as an Add on Therapy With Closed Loop Control in Adolescents With Diabetic Nephropathy
Condition: Type 1 Diabetic Nephropathy
MeSH terms: Kidney Diseases; Diabetic Nephropathies
Study type: Interventional
Phase: Phase 3

Summary: 
      Diabetic nephropathy (DN) is one of the most frequent microvascular complications of diabetes
      mellitus, affecting 25 to 40% of patients with type 1 diabetes (T1DM). Early diagnosis,
      appropriate patient follow-up and treatment are essential to improve the outcomes. There is a
      need for improvements in insulin therapy for people with T1DM as the majority of patients are
      struggling to achieve glycemic targets. Technological advancements and oral adjuncts to
      insulin therapies are starting to be licensed for the use of people with T1DM.

      Dipeptidyl peptidase-4 (DPP-4), a multifunctional serine protease with a dual function
      (regulatory protease and binding protein), can modulate inflammation and immune cell-mediated
      β-cell destruction. DPP-4 degrades the peptide hormones glucagon-like peptide 1 (GLP-1) and
      gastric inhibitory peptide (GIP). Several studies have suggested that the upregulated DPP-4
      activity is correlated with T1DM pathophysiology.
    

Detailed description: 
      Evidence from preclinical investigation suggests that DPP-4 inhibition may have beneficial
      effects on various metabolic indicators in diabetes. DPP-4 inhibitors, such as sitagliptin,
      have been widely used as outstanding blood glucose-dependent antidiabetic agents for patients
      with type 2 diabetes(T2DM). DPP-4 inhibitors have a lowering effect on the glycemic level and
      were not associated with increasing incidence of adverse events. The reno-protective effects
      of DPP-4 inhibition in diabetic nephropathy could be a consequence of the antidiabetic
      actions of DPP-4 inhibitors.

      A second-generation advanced hybrid closed loop ( AHCL) system has been developed to further
      improve glycemic control and usability, with adjustable target glucose and automated
      correction boluses. This system provides proportional integral derivate (PID) algorithm with
      insulin feedback with adaptive insulin limits and model based auto-corrections located on the
      pump. Sitagliptin demonstrated an overall decrease in blood glucose concentrations in adults
      with T1DM when used as an adjunct therapy with an insulin only closed loop (CL) system.

      Stromal cell-derived factor-1 (SDF-1) is ubiquitously expressed in diverse organs and has
      multiple functions. SDF-1 is cleaved and inactivated by the DPP-4 enzyme. The DPP-4 enzyme is
      highly expressed in the kidney. It has been suggested that renal SDF-1 upregulation by DPP-4
      inhibition produces multiple protective actions on the diabetic kidney.

      In view of these data, the investigators assessed the impact of sitagliptin as add on therapy
      with closed loop control in adolescents with T1DM on glycemic control, diabetic nephropathy
      and SDF-1 as a marker for nephropathy.
    

Intervention name(s): oral sitagliptin supplementation
Intervention type(s): Drug
Intervention description(s): oral sitagliptin supplementation for three months
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 1 diabetes; Diabetic nephropathy; Sitagliptin; Time in Range; Advanced hybrid closed system; Stromal cell-derived factor-1 (SDF-1)