Does Dapagliflozin Promote Favorable Health Benefits That Are Independent Of Weight Loss?
Condition: Weight Loss
MeSH terms: Body Weight; Weight Loss
Intervention: Dapagliflozin; Placebo; Weight maintenance; Ad libitum dietary intake; Dietary restriction
Intervention MeSH terms: Dapagliflozin
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Th mechanism of action of dapagliflozin is via sodium-glucose co-transporter 2 (SGLT2)
      inhibition. Sodium-glucose co-transporter 2 inhibition is associated with moderate weight
      (fat) loss, in addition to other health benefits, including decreased blood pressure,
      decreased inflammation, and decreased oxidative stress. It is unclear as to whether these
      health benefits are due to SGLT2 inhibition per se, or as a secondary effect of weight loss.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of informed consent prior to any study specific procedures.

          2. Aged 18-65 years.

          3. No known Type 2 Diabetes

          4. Body mass index greater than or equal to 27.5 kg/m^2

          5. Sedentary (maximum of 2/week regularly scheduled activity sessions of < 20 minutes
             during the previous 2 years)

          6. Completion of a screening visit consisting of medical history, physical examination,
             and 12-lead electrocardiogram and blood pressure assessment at rest and during
             incremental exercise to volitional exhaustion (Note: Subjects with abnormal screening
             values may be eligible if the results are not clinically significant, as judged by the
             investigator or medical monitor)

          7. Agree to abide by the study schedule and dietary restrictions and to return for the
             required assessments

          8. Women of childbearing potential must have negative pregnancy test and be using
             acceptable contraception

        Exclusion Criteria:

          1. Evidence of clinically significant cardiovascular, respiratory, renal, hepatic,
             pulmonary, gastrointestinal, haematological, neurological, psychiatric, or other
             disease that may interfere with the objectives of the study or the safety of the
             subject, as judged by the investigator in agreement with the sponsor or medical
             monitor, have been hospitalized in the past 2 years as a result of these conditions,
             or are receiving pharmacological treatment for these conditions

          2. Use of prescription drugs (see exceptions listed below) or herbal preparations in the
             4 weeks before study commencement.

             Permitted Prescription Drugs

               -  Birth Control

               -  Less than 7 days, short course antibiotics. Note: Rifampin is not permitted.

               -  Other medicines, for Gastroesophageal Reflux Disease (GERD), depression, seasonal
                  allergies and over-the-counter analgesics, maybe allowed, but will be approved on
                  a case-by-case basis.

          3. Is currently enrolled in another clinical study for another investigational drug or
             has taken any other investigational drug within 30 days before the screening visit.

          4. Habitual and/or recent use (within 2 years) of tobacco

          5. Being considered unsuitable for participation in this trial for any reason, as judged
             by the investigator or medical monitor.

          6. History of serious hypersensitivity reaction to dapagliflozin

          7. Severe renal impairment, end-stage renal disease, or dialysis

          8. Pregnant or breastfeeding patients

          9. Severe hepatic insufficiency and/or significant abnormal liver function defined as
             aspartate aminotransferase (AST) >3x upper limit of normal and/or alanine
             aminotransferase (ALT) >3x upper limit of normal

         10. Total bilirubin >2.0 mg/dL (34.2 umol/L)

         11. Positive serologic evidence of current infectious liver disease including Hepatitis B
             viral antibody Immunoglobulin M, Hepatitis B surface antigen and Hepatitis C virus
             antibody

         12. Estimated Glomerular Filtration Rate <60 mL/min/1.73 m^2 (calculated by
             Cockcroft-Gault formula).

         13. History of bladder cancer

         14. Recent cardiovascular events in a patient, including any of the following: acute
             coronary syndrome within 2 months prior to enrollment; hospitalization for unstable
             angina or acute myocardial infarction within 2 months prior to enrollment; acute
             stroke or trans-ischemic attack within two months prior to enrollment; less than two
             months post coronary artery revascularization; congestive heart failure defined as New
             York Heart Association class IV,unstable or acute congestive heart failure. Note:
             eligible patients with congestive heart failure, especially those who are on diuretic
             therapy, should have careful monitoring of their volume status throughout the study

         15. Blood pressure at enrolment: Systolic blood pressure ≥165 mmHg and/or diastolic blood
             pressure ≥100 mmHg

         16. Blood pressure at randomization: Systolic blood pressure ≥165 mmHg and/or diastolic
             blood pressure ≥100 mmHg

         17. Patients who, in the judgment of the medical monitor, may be at risk for dehydration