Dapagliflozin and Measures of Cardiovascular Autonomic Function in Patients With Type 2 Diabetes (T2D)
Condition: Type2 Diabetes; Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin; Glimepiride
Intervention description: Dapagliflozin is a sodium glucose transporter-2 (SGLT-2) inhibitor, a new class of glucose lowering agent that reduces hyperglycemia in patients with T2D by reducing renal glucose reabsorption.; Glimepiride is a sulfonylurea agent that reduces hyperglycemia in patients with T2D by stimulating insulin release from the pancreatic beta cells and reduction of glucose output from the liver.
Intervention MeSH terms: Dapagliflozin; Glimepiride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Masking description: Randomization will be performed by the research Pharmacy. The study coordinator will not be blind to the randomization so that they can adequately discuss the medication with the participant. The study investigator will be blind to the randomization so as to not introduce bias in data qualification.
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the effect of dapagliflozin, a FDA approved diabetes
      medication, on measures of nervous system function of the heart in patients with type 2
      diabetes. The investigators will compare the effect of dapagliflozin with an active
      comparator, glimepiride (a different FDA approved diabetes medication) on measures of heart
      rate variability and assess whether dapagliflozin has modulating effects on measures of
      nervous system function of the heart. This is a crossover study design where all participants
      will receive both study medications equally (12-week intervention periods) in a certain
      order.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with type 2 diabetes as defined on background metformin monotherapy who are
             not meeting ADA standard of care recommended glucose target.

          2. Age ≥18 years

        Exclusion Criteria:

          1. History of multiple urinary tract infections

          2. Patients with mycotic infections especially genital infections.

          3. Patients at risk for volume depletion due to co-existing conditions or concomitant
             medications, such as loop diuretics should have careful monitoring of their volume
             status. This is listed as exclusion criteria but then it says that they just need
             careful monitoring. Is it an exclusion or not?

          4. Severely hypotensive patients

          5. History of unexplained microscopic or gross hematuria, or microscopic hematuria at
             visit 1, confirmed by a follow-up sample at next scheduled visit.

          6. Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g.
             anaphylaxis, angioedema, exfoliative skin conditions

          7. Inability or refusal to comply with protocol

          8. Current participation or participation in an experimental drug study in the previous
             three months

          9. History of diabetic ketoacidosis

         10. Planned cardiac surgery or angioplasty within 3 months

         11. Recent history of acute CV events such as MI, stroke, PAD within 3 months prior to
             enrollment

         12. Patients with severe renal impairment or unstable or rapidly progressing renal disease
             or end stage renal disease.

         13. Clinical conditions that could interfere with the cardiovascular autonomic function
             and heart rate variability (arrhythmias)

         14. Severe hepatic insufficiency and/or significant abnormal liver function (defined as
             aspartate aminotransferase >3× upper limit of normal (ULN) and/or alanine
             aminotransferase >3× ULN) or creatinine kinase >3× ULN.

         15. History of cancer other than basal cell carcinoma and/or treatment for cancer within
             the last 5 years

         16. Women of child-bearing potential who may be pregnant or lactating.

         17. History of pancreas, kidney or liver transplant

         18. History of drug or alcohol abuse

         19. History of allergy to sulfa drugs

         20. Presence of any condition that, in the opinion of the investigator would make it
             unlikely for the subject to complete the study

         21. Congestive heart failure (CHF) defined as New York Heart Association class III and IV