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.
This is a randomized, prospective, placebo-controlled, double-blind, repeated measures study.
92 overweight/obese adults (body mas index > 27.5 kg/m^2) will be recruited for participation
and randomly assigned to one of four 12 week treatments: 1) daily oral administration of
dapagliflozin with ad-libitum dietary intake; 2) daily oral administration of dapagliflozin
with supplemented dietary intake to achieve weight maintenance; 3) daily oral administration
of a placebo plus dietary restriction such that weight loss is matched to participants in
treatment 1; or, 4) daily oral administration of a placebo with ad-libitum dietary intake.
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
8. Women of childbearing potential must have negative pregnancy test and be using
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
12. Estimated Glomerular Filtration Rate <60 mL/min/1.73 m^2 (calculated by
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