Unidad de Investigación Médica en Enfermedades Endocrinas, Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Cuauhtémoc 330, Doctores, 06720, Mexico City, Mexico.
Servicio de Endocrinología, Hospital de Especialidades Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Cuauhtémoc 330, Doctores, 06720, Mexico City, Mexico.
Trials. 2020 Feb 14;21(1):186. doi: 10.1186/s13063-020-4121-x.
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.
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/m). 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.
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.
Clinicaltrials.gov, ID: NCT03968224. Retrospectively registered on May 29, 2019.
墨西哥是全世界肥胖症患病率最高的国家之一。需要有新的专注于 III 类肥胖人群的药理学策略。二甲双胍和达格列净是两种已批准用于治疗糖尿病的药物。除了对葡萄糖的作用外，一些研究还表明二甲双胍可导致体重减轻。在患有糖尿病的患者中，达格列净治疗与轻度但持续的体重减轻有关。该研究的主要结局是确定在等待减肥手术（包括已接受手术的患者）的 III 类肥胖和前驱糖尿病患者中，达格列净和二甲双胍联合治疗与二甲双胍单药治疗相比，在减轻体重方面是否更有效。我们还旨在评估这种联合治疗对腰围、甘油三酯、血压和炎症细胞因子的影响。
这是一项随机的四期临床试验，将纳入年龄在 18 至 60 岁之间且患有 III 级肥胖症（定义为体重指数≥40kg/m²）的糖尿病或前驱糖尿病患者。将排除使用胰岛素的患者。受试者将随机分为两组之一：1）二甲双胍片 850mg，每日两次口服；或 2）二甲双胍片 850mg，每日两次口服加达格列净片 10mg，每日一次口服。需要 108 例患者，可允许 20%的脱落率：二甲双胍组 54 例，二甲双胍/达格列净组 54 例。所有参与者在研究期间将接受个性化的营养咨询。将使用一个为期一个月的导入期来评估治疗方案的耐受性和依从性。在基线和 1、3、6 和 12 个月时记录人体测量和生化变量。在基线时和手术前或 12 个月时（以先发生者为准）采集血清样本以测定胰高血糖素、胃饥饿素、脂联素、抵抗素、白细胞介素 6 和白细胞介素 10。在整个研究过程中记录治疗依从性以及不良事件和次要事件。将采用意向治疗分析。
我们肥胖诊所的 46%的患者被诊断患有前驱糖尿病（32%）或糖尿病（14%）。在该人群中使用达格列净可能会改善体重减轻和其他心血管因素。这种效果可以转化为接受减肥手术之前的时间减少，以及相关合并症的更好控制。
Clinicaltrials.gov，ID：NCT03968224。于 2019 年 5 月 29 日进行回顾性注册。
