Efficacy of the treatment with dapagliflozin and metformin compared to metformin monotherapy for weight loss in patients with class III obesity: a randomized controlled trial

Abstract Background Mexico has one of the highest prevalence rates of obesity worldwide. New pharmacological strategies that focus on people with class III obesity are required. Metformin and dapagliflozin are two drugs approved for the treatment of diabetes. Beyond its effects on glucose, metformin has been suggested by some studies to result in weight loss. Therapy with dapagliflozin is associated with a mild but sustained weight loss in patients with diabetes. The primary outcome of the study is to determine if the combined treatment with dapagliflozin and metformin is more effective than monotherapy with metformin for weight loss in patients with class III obesity and prediabetes or diabetes who are awaiting bariatric surgery (including those patients who do have surgery). We also aimed to assess the effect of this combined treatment on waist circumference, triglycerides, blood pressure, and inflammatory cytokines. Methods This randomized phase IV clinical trial will include patients with diabetes or prediabetes who are between the ages of 18 and 60 years and exhibit grade III obesity (defined as body mass index ≥ 40 kg/m2). Patients using insulin will be excluded. Subjects will be randomized to one of two groups as follows: 1) metformin tablets 850 mg PO bid or 2) metformin tablets 850 mg PO bid plus dapagliflozin tablets 10 mg PO qd. The sample size required is 108 patients, which allows for a 20% dropout rate: 54 patients in the metformin group and 54 in the metformin/dapagliflozin group. All participants will receive personalized nutritional advice during the study. A run-in period of one month will be used to assess tolerance and adherence to treatment regimens. Anthropometric and biochemical variables will be recorded at baseline and at 1, 3, 6, and 12 months. A serum sample to determine glucagon, ghrelin, adiponectin, resistin, interleukin 6, and interleukin 10 will be collected at baseline and before surgery, or at 12 months (whatever happens first). Adherence to treatment and adverse and secondary events will be recorded throughout the study. An intention-to-treat analysis will be used. Discussion Forty-six percent of the patients in our Obesity Clinic have been diagnosed with prediabetes (32%) or diabetes (14%). The use of dapagliflozin in this population could improve weight loss and other cardiovascular factors. This effect could be translated into less time before undergoing bariatric surgery and better control of associated comorbidities. Trial registration Clinicaltrials.gov, ID: NCT03968224. Retrospectively registered on May 29, 2019.