Dapagliflozina

Dapagliflozin is a new oral antidiabetic agent whose mechanism of action increases renal glucose excretion, independently of insulin secretion or insulin action. The efficacy of dapagliflozin is dependent on renal function. The use of dapagliflozin has been licensed to improve glycaemic control in patients with type 2 diabetes mellitus as: - monotherapy when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance. - Add-on combination therapy with other glucose-lowering agents including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. Funding has been restricted to the use of dapagliflozin, prior approval, as dual therapy in combination with metformin. This report aims to assess the efficacy and safety of dapagliflozin in the treatment of type 2 diabetes mellitus, rate the added therapeutic value of dapagliflozin in type 2 diabetes mellitus and identify its current place in therapy. A systematic literature search was carried out, for the purpose of this evaluation, using PubMed, Embase, Cochrane and IDIS databases as well as other secondary sources of evidence-based medicine, therapeutic bulletins and national and international drug agencies. Following the critical reading and analysis of the selected articles, a summary is made out of the scientific evidence available, using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Only one randomised clinical trial, out of the ten trials found, was considered to be a suitable comparison (versus a dual therapy in combination with the sulfonylurea glipizide in patients inadequately controlled with metformin, diet and exercise). No trials have evaluated variables of relevance to patients, except for safety variables. The main efficacy variable in the trials was the change from baseline in HbA1c, except for a study which evaluated the change from baseline in total body weight as main variable. Baseline characteristics of the patients enrolled in the trials significantly differ from those of the population with diabetes in our society which tend to be of an older age and have a longer history of type 2 diabetes mellitus. The major limitation of dapagliflozin derives from its mechanism of action, since its efficacy decreases as renal function declines. The use of dapagliflozin is not recommended in patients with moderate to severe renal impairment ((CrCl<60ml/min or GFG <60 ml/min/1.73 m2) nor in elderly patients, in which a decrease in renal function can be expected. The assessment of safety includes the incidence and rate of discontinuations due to adverse events, episodes of hypoglycaemia, signs or symptoms of genital and urinary tract infections, dehydration, hypovolaemia and hypotension. Further pharmacoepidemiological studies are to be carried out to clarify the long-term effects of dapagliflozin on renal function and the potential effect in the development of breast and bladder tumours. Dapagliflozin as monotherapy has not been evaluated against adequate comparators (sulfonylureas, pioglitazone, gliptins). In combination therapy with metformin, the efficacy of dapagliflozin was shown to be non-inferior to glipizide plus metformin, resulting in a mean reduction of 0.52% in HbA1c, with a difference of 0.00 among both groups (95% CI: -0.11 a 0.11). There are no comparative data against other second-line treatment options. As shown in the studies, the overall incidence of adverse events with dapagliflozin as monotherapy (21.5%) was similar to that observed with placebo, and greater to that observed with metformin (15.4%). Hypoglycaemia of any type was the adverse event more frequently reported. The incidence of severe hypoglycaemic events observed in most of the studies was low. The overall incidence of adverse events observed in the study that compared dapagliflozin+metformin against glipizide+metformin was similar for both groups (27%) and incidence of hypoglycaemic events with dapagliflozin (3.5%) was significantly lower to that observed with glipizide (40.8%). Reductions of body weight of about 2 to 3 kg and a slight decrease in blood pressure (1 to 5 mmHg) have been observed in all studies in the groups treated with dapagliflozin together with diet and exercise. Dosing scheme (every 24 hours) is similar to other oral antidiabetic agents and its cost is similar to that for gliptines and higher to that for sulfonylureas or generic pioglitazone. Funding has been limited to the use of dapagliflozin as dual therapy regimen in combination with metformin as an option for patients with contraindication or intolerance to sulfonylureas, such a those experiencing frequent hypoglycaemic events, weight loss associated risks, as long as they are under 75 years of age and have no moderate to severe renal impairment. In the light of the above, we consider dapagliflozin means no therapeutic innovation in the therapy of type 2 diabetes mellitus over other therapeutic alternatives available.

Sistema de Información de la Coordinación Autonómica de Trasplantes de Andalucía (SICATA) : Subsistema de Insuficiencia Renal Crónica : Informe 2013

Coordinación Autonómica de Trasplantes

Osteoporosis e índice de masa corporal en el trasplantado renal.

INTRODUCTION: frequently after kidney transplantation there is an increase in weight with a resulting high percent of obesity in these recipients. This combined with a rapid loss of bone mass, a higher prevalence of osteoporosis and fractures is evident than in normal populations. OBJECTIVES: to explore the relationship between body mass index (BMI) and prevalence of osteoporosis in a population of renal transplant recipients. METHODS: prospective longitudinal study design. The study was conducted on 306 kidney transplant recipients. The relationship between weigh and body mass index with femoral and lumbar osteopenia and osteoporosis prevalence at the moment of transplant and at 12 months post was explored. RESULTS: there was a high prevalence of overweight (35.6%) and obese (14.1%) recipients after renal transplant and 1 year after (42.2% and 24.2% respectively). Significant differences were found(p = 0.049) between the weight at the time of transplant and the presence of osteopenia or osteoporosis at the lumbar level one year after, the highest weights were in recipients with osteoporosis. The mean BMI was higher (p = 0.028) in osteoporotic patients (26.59 kg/m2) than in patients with osteopenia (24.23 kg/m2). CONCLUSION: results seem to be consistent with recent studies in the general population showing excessive weight as a possible factor detrimental to the bone health.

Estudio longitudinal del síndrome metabólico tras el trasplante renal.

BACKGROUND: The occurence of the metabolic syndrome (MS) between the renal receptors is one of the major complications after transplantation and is associated with an increased risk of graft failure and high rates of obesity and diabetes new appearance. AIMS: This study aims to investigate the prevalence and risk factors associated with the development of the MS and to evaluate the association between the same with the allograft dysfunction. METHODS: The samples consisted of 138 renal transplant patients, 83 men and 55 women, kidney transplant, which was attended by over five years for the transplant consultation. Were analyzed as potential risk factors for MS: age, sex, body mass index (BMI), weight, hypertension, diabetes, LDL, HDL, triglycerides in serum and immunosuppressive therapy (cyclosporine, tacrolimus, mycophenolate mofetil), was also assessed the prevalence of acute rejection episodes and renal function. RESULTS: The prevalence of MS was 39.85 %. As statistically significant risk factors were obtained the BMI, overweight, HDL cholesterol levels, triglycerides and LDL as well as hypertension and diabetes. There were high rates of acute rejection and differences in story to the glomerular filtration rate. CONCLUSIONS: There is a high prevalence of the MS that severely compromised renal function and graft survival in renal transplant patients, it is very important the control and strict monitoring of all risk factors identified.

Thyroid metastasis as initial presentation of clear cell renal carcinoma.

INTRODUCTION Metastatic tumors account for 1.4-2.5% of thyroid malignancies. About 25-30% of patients with clear cell renal carcinoma (CCRC) have distant metastasis at the time of diagnosis, being the thyroid gland a rare localization [5%]. PRESENTATION OF THE CASE A 62-year woman who underwent a cervical ultrasonography and a PAAF biopsy reporting atypical follicular proliferation with a few intranuclear vacuoles "suggestive" of thyroid papillary cancer in the context of a multinodular goiter was reported. A total thyroidectomy was performed and the histology of a clear cell renal carcinoma (CCRC) was described in four nodules of the thyroid gland. A CT scan was performed and a renal giant right tumor was found. The patient underwent an eventful radical right nephrectomy and the diagnosis of CCRC was confirmed. DISCUSSION Thyroid metastasis (TM) from CCRC are usually apparent in a metachronic context during the follow-up of a treated primary (even many years after) but may sometimes be present at the same time than the primary renal tumor. Our case is exceptional because the TM was the first evidence of the CCRC, which was subsequently diagnosed and treated. CONCLUSION The possibility of finding of an incidental metastatic tumor in the thyroid gland from a previous unknown and non-diganosed primary (as CCRC in our case was) is rare and account only for less than 1% of malignancies. Nonetheless, the thyroid gland is a frequent site of metastasis and the presence of "de novo" thyroid nodules in oncologic patients must be always considered and studied.