Effect of Saxagliptin and Dapagliflozin on Endothelial Progenitor Cell in Patients With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2; Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin 10mg; Saxagliptin 5mg; Placebo Oral Tablet
Intervention description: Dapagliflozin 10mg PO QD; Saxagliptin 5 mg PO QD; Matching Placebo Tablets
Intervention MeSH terms: Dapagliflozin; Saxagliptin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 15.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: saxagliptin dapagliflozin diabetes cardiovascular diseases EPC

Summary:

      The Investigator hypothesize that Dapagliflozin will improve EPC number and function AND
      Saxagliptin in addition to Dapagliflozin (additive effect) may improve EPC number and
      function even more than Dapa alone, compared to placebo.

      The Investigator propose a 3-arm randomized, parallel group, longitudinal study of 16-week
      intervention duration. Participants will be randomized to 3 groups:

      Group A: Dapa (10 mg) + Saxa Placebo, Enroll n=15, retain n=12 Group B: Dapa (10 mg) + Saxa
      (5 mg), Enroll n=15, retain n=12 Group C: Dapa Placebo + Saxa Placebo, Enroll n=15, retain
      n=12
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to understand the study, and provide a signed & dated informed consent.

          2. Diagnosis of Type 2 diabetes mellitus using criteria of the American Diabetes
             Association.

          3. 30-70 years old.

          4. HbA1C 7 to 10%, both inclusive

          5. BMI of 25 - 39.9 kg/m2 both inclusive.

          6. Taking a stable dose (for 12 weeks) of Metformin (any dosage) and/or Insulin (any
             dosage) for the treatment of T2DM

          7. Patients with current Cardiovascular Disease (CVD) in tye 2 diabetes patients, defined
             by ≥ 1 of the following:

               1. MI >2 months prior

               2. Multivessel CAD

               3. Angina (intermittent or chronic)

               4. Single vessel CAD with positive stress test or UA hospitalization in prior year

               5. UA >2 months prior and evidence of CAD

               6. Stroke >2 months prior

               7. Occlusive PAD

               8. Proteinuria of more than 30mg/dl

        Exclusion Criteria:

          1. Planned CV surgery or angioplasty in 1 month

          2. Prior surgery with chronic malabsorption (eg, bariatric) in prior 1 year

          3. Diagnosis of Type 1 diabetes mellitus

          4. History of GAD antibody positive status

          5. Uncontrolled Inflammatory Disease/Inflammatory drug use. **Evaluated by PI on
             case-by-case basis**

          6. Recent history of diabetic keto-acidosis in the past 3months, or recurrent history of
             diabetic ketoacidosis (≥ 3 times)

          7. Active bladder cancer

          8. Active wounds (e.g. Diabetic ulcers) or recent surgery within 1 month

          9. Untreated hyper/hypothyroidism

         10. Women of child bearing potential who are not willing to use a contraceptive method to
             avoid pregnancy for the 16 weeks of study duration

         11. Women who are pregnant or breastfeeding

         12. Implanted devices (eg. Pacemaker) that may interact with Tanita scale

         13. Any other clinical condition that would jeopardize patients safety while participating
             in this clinical trial Concomitant Medications

         14. Taking any other oral anti-diabetic agent other than Metformin and/or Insulin for
             their treatment of T2DM

         15. Beginning statin medications in the past 1 month or change in statin dose in the past
             1 month

         16. Use of consistent long-term steroid medication (oral, inhaled, injected) within the
             last 1 month

         17. Treatment with a strong cytochrome P450 3A4 (CYP34A) or P-gp inducer (ie. Rifampin)

         18. Subjects with a history of any serious hypersensitivity reaction to Dapagliflozin /
             Saxagliptin or another SGLT-2 inhibitor/ DPP4 inhibitor Laboratory Findings

         19. Uncontrolled hyperglycemia, defined as a fasting glucose >240 mg/dL (>13.3 mmol/L) at
             screening.

         20. Liver disease with ALT, AST or ALP x3 ULN

         21. eGFR < 60 mL/min/1.73 m2 by MDRD equation in the past 3 months

         22. Clinically significant RBC disorders such as hemoglobinopathies

         23. Serum creatinine levels ≥1.8 mg/dL with estimated eGFP < 60 mL/min

         24. Triglycerides > 450 mg/dL

         25. Baseline Hematuria (judged by a urinalysis dipstick at screening) Social History

         26. Active smokers

         27. Chronic or persistent alcohol or drug abuse

         28. Prisoners or subjects who are involuntarily incarcerated

         29. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg. infectious disease) illness

         30. Participation in another trial with an investigational drug within 30 days prior to
             informed consent