Linagliptin's Effect on CD34+ Stem Cells
Condition: Type 2 Diabetes; Impaired Renal Function
MeSH terms: Renal Insufficiency; Diabetes Mellitus, Type 2
Intervention: Linagliptin; Placebo
Intervention description: 5 mg tablet once daily for 12 weeks; 1 tablet daily for 12 weeks
Intervention MeSH terms: Linagliptin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus, Type 2; Endothelial cells; Cellular biomarker; endothelial dysfunction; CD34+; Impaired renal function

Summary:

      Type 2 diabetes is a national epidemic. Diabetes has undesirable effects on blood vessels
      which may contribute to heart disease. Endothelial Progenitor Cells (EPCs) are found in the
      blood. Research has shown that improving the survival of these special blood cells may
      decrease the harmful effects of diabetes on blood vessels and reduce or reverse heart
      disease. Linagliptin is an Food and Drug Administration (FDA) approved prescription medicine
      used along with insulin or with oral medications to lower blood sugar in people with Type 2
      diabetes. It is in a class of diabetes medication called Dipeptidyl peptidase-4 (DPP-4)
      inhibitors. DPP-4 inhibitors have been shown to increase EPCs in patients with Type 2
      diabetes.

      Hypothesis: Both type 2 diabetes and Chronic Kidney Disease (CKD) are associated with poor
      stem cell number and function. Poor viability and function of EPCs in CKD and diabetes The
      investigators hypothesize that use of Linagliptin (along with Insulin) may help reduce
      cardiovascular risk by improving EPC survival and function above and beyond adequate glucose
      metabolism control
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults aged 30-70 years

          -  Diagnosis of type 2 diabetes within the previous 15 years using criteria of the
             American Diabetes Association

          -  Currently being treated with 1-2 grams/day of metformin, or insulin or both stably

          -  Hemoglobin A1c (HbA1C) between 6.5% to 10.0% (both inclusive)

          -  Body Mass Index (BMI) between 25 and 39.9 kg/m2 (both inclusive)

          -  Chronic Kidney disease (CKD) Stages 1-3, Creatinine clearance (CrCl) less than 90 and
             more than 29

        Exclusion Criteria:

          -  Type 1 diabetes

          -  History of Diabetic Ketoacidosis (DKA) or hyperosmolar nonketotic coma

          -  Hemoglobinopathies with low hematocrit (Below 28 Units)

          -  History of pancreatitis

          -  History of cancer within the past 5 years (except basal cell carcinoma)

          -  Previous cardiovascular or cerebrovascular event within 6 months of screening or
             active or clinically significant coronary and/or Peripheral Vascular Disease (PVD)

          -  Statin use started in the last 3 month

          -  Current use of oral or injectable anti-diabetic medication other than Metformin and
             insulin

          -  Consistent use of steroids within the last 3 months

          -  Any active wounds, or surgery within the past 3 months

          -  Inflammatory disease, or the chronic use of anti-inflammatory drugs within the past 3
             months

          -  Untreated hyper/hypothyroidism

          -  Contraindications to moderate exercise

          -  Implanted devices that might interact with the tanita scale

          -  Pre-existing liver disease and/or Alanine aminotransferase (ALT) and Aspartate
             Aminotransferase (AST) > 2.5 times Under the Normal Limits (UNL)

          -  Untreated Systolic blood pressure > 140 mmHg or diastolic blood pressure> 90 mmHg

          -  Serum creatinine levels ≥ 2.0

          -  CKD Stages 4 and 5 (estimated CrCl <30 mL/min)

          -  Triglycerides > 450 mg/dL

          -  Known allergies or hypersensitivities to Linagliptin or Dipeptidyl peptidase-4 (DDP-4)
             inhibitors

          -  Treatment with cytochrome p450 (CYP 3A4) inhibitors

          -  Women of child bearing age who are unwilling or unable to use an acceptable method to
             avoid pregnancy for the entire study

          -  Prisoners or subjects that are involuntarily incarcerated

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g. infectious disease) illness

          -  Additionally, patients who are active smokers, patients who are pregnant, nursing
             women, and post-menopausal women who are on hormone replacement therapy will be
             excluded.