Pharmacogenetics of SGLT2 Inhibitors
Condition: Diabetes Mellitus; Gout; Hyperuricemia
MeSH terms: Hyperuricemia
Intervention: Canagliflozin
Intervention description: A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.
Intervention MeSH terms: Canagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: SGLT2; SLC5A2; SLC5A4; SLC5A9; SLC2A9; GLUT9; SGLT3; SGLT4; pharmacogenomics

Summary:

      Sodium-dependent glucose transporter-2 (SGLT2) inhibitors are a new class of anti-diabetic
      drugs, which increase urinary glucose excretion thereby promoting weight loss and decreasing
      plasma glucose levels. We hypothesize that the pharmacodynamic response to SGLT2 inhibitors
      (specifically canagliflozin) varies among individuals, and that a proportion of this
      inter-individual variation can be explained by genetic variation. This is a pilot study in
      healthy, non-diabetic subjects in whom glucose and other related metabolites in the urine and
      plasma will be measured before and after administration of a single dose of canagliflozin.
      This will allow us to characterize the inter-individual variation in the pharmacodynamic
      response to canagliflozin as well as determine if changes in glucose and other related
      metabolite levels are associated with variants in various candidate genes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Of Amish descent

          -  Age 21 or older

          -  BMI 18-40 kg/m2

        Exclusion Criteria:

          -  Known allergy to canagliflozin

          -  History of diabetes, random glucose greater than 200 mg/dL, or HbA1c greater than or
             equal to 6.5%

          -  Currently taking diuretics, antihypertensive medication, uric acid lowering
             medications, or other medication that the investigator judges will make interpretation
             of the results difficult

          -  Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or
             other diseases that the investigator judges will make interpretation of the results
             difficult or increase the risk of participation

          -  Seizure disorder

          -  Positive urine human chorionic gonadotropin (hCG) test or known pregnancy within 3
             months of the start of the study

          -  Estimated glomerular filtration rate less than 60 mL/min

          -  Currently breast feeding or breast feeding within 3 month of the start of the study

          -  Liver function tests greater than 2 times the upper limit of normal

          -  Hematocrit less than 35%

          -  Currently symptomatic for urinary tract or yeast infection or history of two or more
             urinary tract or yeast infections in the past 12 months.

          -  Abnormal thyroid stimulating hormone (TSH)