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Occurrence of Bisphenol A and its analogues in some foodstuff marketed in Europe.
Russo, G, Barbato, F, Mita, DG, Grumetto, L
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2019;:110575
Abstract
Bisphenol A and its analogues belong to the class of endocrine disrupting chemicals, massively employed by industries to produce polycarbonate and epoxy resins, designed to be in direct contact with foodstuffs. Their leaching from the canned packaging into its content results in food contamination. This review aims at offering a country-specific overview of the occurrence of bisphenols in six main categories of foodstuff marketed in the EU, based on monitoring studies performed in the 27 EU countries for which data are available and prevalently published in the last five years. The general overview of the literature data shows that concentration values of BPs detected into foodstuff is lower in Northern Europe than Southern Europe. A probable daily intake was hypothesized for some countries to provide an EU population exposure assessment. The consumption of canned meat and vegetables is responsible of PDI values higher than those of other food categories. These data emphasize that food and beverage monitoring should deserve greater attention especially by European countries for which no studies are available and especially with regards to bisphenols other than BPA whose limits are not set by the European regulations and whose toxicity has not been fully established.
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Dietary Predictors of Phthalate and Bisphenol Exposures in Pregnant Women.
Pacyga, DC, Sathyanarayana, S, Strakovsky, RS
Advances in nutrition (Bethesda, Md.). 2019;(5):803-815
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Abstract
Endocrine disrupting chemicals (EDCs) can disrupt fetal developmental processes during pregnancy, leading to long-term adverse outcomes in humans. A major source of exposure to EDCs, such as phthalates and bisphenols, is the food supply, primarily due to contamination from processing and packaging. Therefore, this review aimed to 1) review food-monitoring sources of phthalates and bisphenols, and 2) evaluate methodologies and provide future directions needed to establish EDC-limiting dietary recommendations in pregnancy. Using PubMed, 10 peer-reviewed studies were found on dietary predictors of EDC exposure in pregnancy, and all were selected for review. Use of plastic containers in pregnancy was associated with higher urinary phthalate metabolites, whereas canned food consumption was associated with higher urinary bisphenol A (BPA) concentrations. Foods and dietary patterns associated with healthier food choices (e.g., organic/grown/raised/caught foods, folic acid supplements, vegetarianism) were generally associated with lower urinary phthalate metabolite and BPA concentrations. Despite the many food-monitoring studies reporting high BPA and phthalate concentrations in various foods, the designs of most studies described here were not sufficiently robust to consistently detect associations of specific foods/food groups with phthalates and BPA. Given the limitations of currently available research, future studies should incorporate more valid questionnaires to accurately assess dietary EDC exposure, strive for concurrent diet and exposure assessment, and assess whether geographical and cultural differences modify associations of diet with gestational EDC exposures. Such progress will be critical for developing dietary recommendations that ensure the safety and health of pregnant women.
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A complete review of empagliflozin: Most specific and potent SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus.
Chawla, G, Chaudhary, KK
Diabetes & metabolic syndrome. 2019;(3):2001-2008
Abstract
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest class of drugs to be introduced for the treatment of type 2 diabetes mellitus (T2DM). They reduce hyperglycemia by increasing urinary glucose excretion and exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin is a potent SGLT2 inhibitor used to improve glycemic control in adults with T2DM. It has the highest SGLT2 specificity among all the clinically used or currently tested SGLT2 inhibitors. Low risk of hypoglycemia, absence of weight gain and demonstrated cardiovascular risk reduction support its consideration as a first line medication in addition to metformin for patients with T2DM and cardiovascular disease. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. This review covers the complete information on empagliflozin including the history of its development, synthesis, pharmacology and different methods which have been reported for its analysis.
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Novel Antidiabetic Therapies and Cardiovascular Risk Reduction: The Role of the Noninferiority Trial.
Thompson, J, Schacht, S, Rothenberg, F
Cardiology clinics. 2019;(3):335-343
Abstract
Diabetes is a major risk factor for cardiovascular disease, yet until now treatments for diabetes had only a modest impact on cardiovascular events. New interventions for patients with type 2 diabetes mellitus (oral empagliflozin and injectable liraglutide) are associated with unprecedented reductions in composite cardiovascular outcomes that seem disproportionate to the impact on glycated hemoglobin. This review examines in detail the recent trials that arrived at these conclusions, limitations of these studies, and how these outcomes may influence patient management in the future.
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Effect of empagliflozin beyond glycemic control: Cardiovascular benefit in patients with type 2 diabetes and established cardiovascular disease.
Monteiro, P, Aguiar, C, Matos, P, Silva-Nunes, J, Birne, R, Branco, P, Calado, J, Melo, M, Polónia, J
Revista portuguesa de cardiologia. 2019;(10):721-735
Abstract
The prevalence of type 2 diabetes (T2D) continues to increase, and its association with cardiovascular (CV) disease has led to the inclusion of CV endpoints in clinical trials on the treatment of T2D. This article explores the various trials already performed and under development in this field, with particular focus on the EMPA-REG OUTCOME trial. In this trial, empagliflozin, a sodium-glucose co-transporter 2 inhibitor, demonstrated a reduction in CV risk in patients with T2D and established CV disease, in addition to CV safety and a decrease in glycated hemoglobin. This represents a paradigm shift that has led to changes in the international guidelines for the treatment of T2D. These results were maintained in subsequent subgroup analysis for heart failure, chronic kidney disease and peripheral arterial disease, although there are many questions concerning the mechanisms involved in these effects, including whether they are hemodynamic, metabolic or due to decreased myocardial cytoplasmic sodium concentrations. With this reduction in risk for major CV events in patients with T2D, the EMPA-REG OUTCOME trial demonstrated CV protection from a hypoglycemic drug for the first time, and opened a new era in the treatment and management of T2D. This study has led to the development of ongoing trials that will establish which patients will benefit most from this therapy, particularly with regard to comorbidities.
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Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes.
Coppenrath, VA, Hydery, T
The Annals of pharmacotherapy. 2018;(1):78-85
Abstract
OBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) tablets. DATA SOURCES Searches of MEDLINE (1946 to July 1, 2017) were conducted using the keywords QTERN, saxagliptin, and dapagliflozin. Additional data were obtained from the prescribing information, the product dossier, and Clinicaltrials.gov . STUDY SELECTION AND DATA EXTRACTION All English language articles related to pharmacology, pharmacokinetics, efficacy, or safety of the combination therapy in human subjects were reviewed. DATA SYNTHESIS The pharmacokinetics of saxagliptin and dapagliflozin were not affected significantly when administered as an FDC product. Saxagliptin may suppress the increased secretion of glucagon associated with dapagliflozin. The combination dapagliflozin/saxagliptin has been studied as add-on therapy to metformin in patients with uncontrolled type 2 diabetes mellitus (T2DM). The difference in hemoglobin A1C (A1C) between saxagliptin + dapagliflozin + metformin (triple therapy) and saxagliptin + metformin was -0.59 (95% CI = -0.81 to -0.37, P < 0.0001), and the difference between triple therapy and dapagliflozin + metformin was -0.27 (95% CI = -0.48 to -0.05, P = 0.0166). The combination was well tolerated when added to metformin. CONCLUSION QTERN (dapagliflozin/saxagliptin) tablets are a reasonable option for patients with T2DM not controlled on metformin, but cost, insurance coverage, and a lackluster reduction in A1C will likely limit its use until more data regarding its effects on complications of diabetes and cardiovascular outcomes become available.
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Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials.
Jabbour, S, Seufert, J, Scheen, A, Bailey, CJ, Karup, C, Langkilde, AM
Diabetes, obesity & metabolism. 2018;(3):620-628
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Abstract
AIM: To evaluate the safety and tolerability of dapagliflozin, a highly selective sodium-glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS Data were pooled from 13 placebo-controlled trials of up to 24 weeks' duration (dapagliflozin, n = 2360; placebo, n = 2295). Larger placebo-/comparator-controlled pools of 21 (≤208 weeks; dapagliflozin, n = 5936; control, n = 3403) and 30 trials (≥12 weeks; dapagliflozin, n = 9195; control, n = 4629) assessed the rare adverse events (AEs) of diabetic ketoacidosis (DKA) and lower limb amputation, respectively. RESULTS Over 24 weeks, the overall incidence of AEs and serious AEs (SAEs) was similar for dapagliflozin and placebo: 60.0% vs 55.7% and 5.1% vs 5.4%, respectively. Rates of hypoglycaemia, volume depletion AEs, urinary tract infections (UTIs) and fractures were balanced between the groups. Genital infections were more frequent with dapagliflozin (5.5%) vs placebo (0.6%) and renal function AEs occurred in 3.2% vs 1.8% of patients (the most common renal AE was decreased creatinine clearance: 1.1% vs 0.7%). In the 21-study pool, 1 SAE of DKA and 3 AEs of ketonuria/metabolic acidosis occurred with dapagliflozin vs none with control; estimated combined incidence for these events was 0.03% (95% confidence interval 0.010-0.089). In the 30-study pool, lower limb amputation occurred in 8 (0.1%) and 7 (0.2%) patients receiving dapagliflozin and control, respectively. CONCLUSION The overall incidence rates of AEs and SAEs were similar in the dapagliflozin and placebo/control groups, including the incidence of hypoglycaemia, volume depletion, fractures, UTIs, amputations and DKA. Genital infections were more frequent with dapagliflozin than placebo.
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Sodium-Glucose Cotransporter-2 Inhibition in Type 2 Diabetes Mellitus: A Review of Large-Scale Cardiovascular Outcome Studies and Possible Mechanisms of Benefit.
Dalan, R
Cardiology in review. 2018;(6):312-320
Abstract
Cardiovascular (CV) disease remains the leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). However, conventional antihyperglycemic medications seem to have minimal effect on lowering CV risk despite achieving excellent reductions in glycated hemoglobin A1c and associated reductions in microvascular risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as noteworthy antihyperglycemic agents with concomitant CV and renal protection in T2DM patients. In this comprehensive review, we present the key CV findings from major large-scale outcome trials of SGLT2 inhibitors to date. We also review the mechanistic studies that might explain the CV benefits of SGLT2 inhibition in patients with T2DM.
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Benefits of SGLT2 Inhibitors Beyond Glycemic Control - A Focus on Metabolic, Cardiovascular and Renal Outcomes.
Minze, MG, Will, KJ, Terrell, BT, Black, RL, Irons, BK
Current diabetes reviews. 2018;(6):509-517
Abstract
BACKGROUND Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new pharmacotherapeutic class for the treatment of Type 2 Diabetes Mellitus (T2DM). OBJECTIVE To evaluate beneficial effects of the SGLT2 inhibitors on metabolic, cardiovascular, and renal outcomes. METHODS A Pub-Med search (1966 to July 2017) was performed of published English articles using keywords sodium-glucose co-transporter 2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin. A review of literature citations provided further references. The search identified 17 clinical trials and 2 meta-analyses with outcomes of weight loss and blood pressure reduction with dapagliflozin, canagliflozin, or empagliflozin. Three randomized trials focused on either empagliflozin or canagliflozin and reduction of cardiovascular disease and progression of renal disease. RESULTS SGLT2 inhibitors have a beneficial profile in the treatment of T2DM. They have evidence of reducing weight between 2.9 kilograms when used as monotherapy to 4.7 kilograms when used in combination with metformin, and reducing systolic blood pressure between 3 to 5 mmHg and reducing diastolic blood pressure approximately 2 mmHg. To date, reduction of cardiovascular events was seen specifically with empagliflozin in patients with T2DM and a history of cardiovascular disease. In the same population, empagliflozin was associated with slowing the progression of kidney disease. Moreover, patients with increased risk of cardiovascular disease treated with canagliflozin have decreased risk of death from cardiovascular causes, nonfatal MI, or nonfatal stroke. Data regarding these outcomes with dapagliflozin are underway. CONCLUSION SGLT2 inhibitors demonstrate some positive metabolic effects. In addition, empagliflozin specifically has demonstrated reduction in cardiovascular events and delay in the progression of kidney disease in patients with T2DM and a history of cardiovascular disease. Further data is needed to assess if this is a class effect.
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Diabetic kidney disease in 2017: A new era in therapeutics for diabetic kidney disease.
Wanner, C
Nature reviews. Nephrology. 2018;(2):78-80