Following written consent, all study patients will undergo the following clinical, metabolic and laboratory evaluations before and during treatment. To ensure that patients remain unidentified, all study subjects will be assigned an individual study identifier which includes the study acronym, patient initials, and unique number. All blood samples will be obtained and results identified and reported using this unique study identifier. A full physical examination will be performed and vital signs (blood pressure, respiration and temperature) determined. Trained personnel using standardized protocols at the baseline and follow-up examination will obtain anthropometric measurements and blood specimens. Absolute body weight, height, waist and hip circumference, body fat distribution (waist/hip {WHR}) and waist/height ratio ({WHtR}) and blood pressure (BP) will be determined. Body weight will be measured to the nearest 0.1 kg using a calibrated digital scale with participants in light clothing and no shoes. Height will be measured to the nearest centimeter. The total body adiposity (total fatness), defined as the accumulation of body fat without regard to regional distribution, will be expressed as BMI and calculated as weight (kg)/ height (m) 2. The circumference measurements will be taken in the upright position using a 15-mm width flexible metric tape held close to the body but not tight enough to indent the skin. Waist circumference (WC) will be measured at the narrowest level midway between the lowest ribs and the iliac crest and hip circumference measured at the widest level over the buttocks while the subjects are standing and breathing normally. The WHR and WHtR will be calculated for measure of body fat distribution.
All patients will randomly be assigned to one of 3 medication treatment groups-- dapagliflozin-metformin (DAP-MET; 5 mg DAP/ MET 1000 mg BID), metformin XR (MET 1000 mg BID) or dapagliflozin (DAP 10 mg QD); all subjects will be allocated to one of these 3 groups based on computer-generated random numbers using a block randomization method. Oral glucose tolerance tests (OGTTs) with glucose (G) and insulin (I) measured at 0, 30, 60, and 120 after glucose load to assess diabetes, fasting (FBG) and mean blood glucose (MBG) concentrations, insulin resistance and pancreatic ß-cell function will be performed prior to randomization and at 20-24 weeks after full doses of study medications are reached. Mean blood glucose (MBG) concentrations will be calculated by summing glucose values obtained at 0,30,60 and 120 minutes during the OGTT and dividing by 4. At the initial lab evaluation, creatinine and calculated eGFR, TSH, and ß-hCG will be determined for study inclusion. Baseline blood samples will also be analyzed for lipid profiles and liver enzymes.
All patients will receive the same counseling concerning the benefits of lifestyle modification through diet and exercise. The patients will be also encouraged to increase daily exercise (such as walking, using stairs), although this will not be formally assessed. The participants will receive further encouragement to adhere to the regime during follow-up phone calls. Side effects of the treatment and reason for any withdrawals from the study will be recorded.
