Effectiveness of Dapagliflozin for Weight Loss

Methods:

A convenience sampling will be done for patients diagnosed with diabetes or prediabetes according to the American Diabetes Association (ADA) criteria, who assist to the Obesity Clinic and meet the selection criteria. Data from patients that during the study protocol are called to undergo bariatric surgery procedure will be used until the time of surgery (intention-to-treat analysis). The prevalence of comorbidities at baseline and the type and dose of drugs used for treatment will be recorded. Patients will be randomized by a random numbers system generated with a computational software and will be assigned to a group: metformin (1,700 mg/day) or metformin (1,700 mg/day) and dapagliflozin 10 mg. All patients will receive dietary treatment and follow-up during the study by the Nutrition Service. Once assigned to the corresponding group, patients will receive an identification code that will be retained throughout the study. One of the researchers not directly involved in patient care, will assign tablets needed for daily intake for a month and then the number of tablets required for 3 months in a sealed envelope. A run-in period will be used to assess tolerance to treatments. This period will be for a month. At this time patients may notice an increase of uresis and will be instructed to increase fluid intake. Anthropometric and biochemical variables will be recorded baseline and at 1, 3, 6 and 12 months. The determination of glucagon, ghrelin, adiponectin, resistin, interleukin 6 (IL-6) and interleukin 10 (IL-10) will be held on initial appointment and before surgery (depending on the response of each patient). For the determination of these cytokines and peptides, an ELISA kit (Enzyme Linked Immunosorbent Assay) will be used. Adherence to treatment will be evaluated and will consist in consumption of 90 percent of pills granted. The patient will be required to return the drug blister. The registration of adverse events will take place from the start of treatment and throughout the study. Each event will be evaluated by researchers and classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 list. CTCAE considers that an adverse event grade 4 or 5 indicates discontinuation of treatment; grade 3 must be submitted to review by the medical team, and grades 1 or 2 require registration and intervention but not discontinuation of treatment. Adverse events will be recorded in the report sheet. An intention-to-treat analysis will be used if patients require treatment with insulin or sulfonylureas (grade 3 adverse event). They will provide information until the time of its inception. Patients who do not achieve weight loss at one year follow-up, will be discarded to their primary care hospital for continue with dietary recommendations.

Sample Size:

A convenience sample will be performed of patients with obesity class III and prediabetes or diabetes according ADA criteria at Obesity Clinic who meet selection criteria. The sample size was calculated using a mean difference formula with data from Zhang et al. who evaluated weight loss in patients using metformin/dapagliflozin and compared with placebo. Sample size required is 90 patients: 45 patients in metformin group and 45 patients in dapagliflozin/metformin group. Considering a loss of 20 percent of population during study, the final sample size required is 108 patients: 54 patients in metformin and 54 patients in dapagliflozin group.

Statistical analysis Quantitative variables will be presented as means and standard deviation or median with interquartile ranges according to data distribution. Qualitative variables will be presented as frequencies or percentages. For assessing data distribution, a Shapiro-Wilk test will be performed. Association between quantitative variables will be assessed through Repeated measures ANOVA and qualitative variables with McNemar test. Statistical significance will be evaluated with p < 0.05. Statistical analysis will be performed using statistical packages: Statistical Package for the Social Sciences (SPSS) version 17.0.