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.

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.

Symptomatic Primary Hyperparathyroidism as a Risk Factor for Differentiated Thyroid Cancer.

BACKGROUND: The primary hyperparathyroidism (PHPT) is a common disease for the endocrinologist. The concomitant thyroid disease and differentiated thyroid cancer (DTC) appear to be more frequent in patients with PHPT than in the general population. The aim of this study was to characterize patients with symptomatic PHPT with and without DTC and analyze frequency and risk factors. METHODS: We consecutively studied patients with symptomatic PHPT diagnosed and treated at our center between 2013 and 2015. Patients with subclinical and syndromic forms of PHPT were excluded. Clinical and biochemical characteristics of patients with and without DTC were compared and risk factors were determined. All patients were studied with thyroid ultrasound and thyroid gammagraphy with TC-MIBI. Two expert surgeons performed all the surgical procedures. RESULTS: In 59 patients included, we found 12 cases of PTC (20.3%). The final histopathological report of the PTC was 7 cases of follicular variant, 2 cases of oncocytic variant, 2 cases of classic variant, and 1 case of columnar cells variant of PTC. Patients with thyroid cancer were older than patients without thyroid cancer (62 ± 9.5 versus 52 ± 15.8, p = 0.03). Higher preoperative levels of iPTH were associated with PTC (p=0.03) [OR 5.16 (95% CI: 1.08-24.7)]. CONCLUSION: PTC is frequent in patients with symptomatic PHPT. Thyroid nodules in patients with symptomatic PHPT must be studied before parathyroidectomy. In symptomatic PHPT, higher level concentration of parathormone (PTH) was associated with higher risk of DTC.