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Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: Design and rationale for the DARE-19 study.
Kosiborod, M, Berwanger, O, Koch, GG, Martinez, F, Mukhtar, O, Verma, S, Chopra, V, Javaheri, A, Ambery, P, Gasparyan, SB, et al
Diabetes, obesity & metabolism. 2021;(4):886-896
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Abstract
AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.
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Low carbohydrate diet while taking dapagliflozin: A case report and review of literature.
Paul, N, Jonklaas, J
Diabetes & metabolic syndrome. 2021;(1):361-363
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Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome.
Elkind-Hirsch, KE, Chappell, N, Seidemann, E, Storment, J, Bellanger, D
The Journal of clinical endocrinology and metabolism. 2021;(10):3019-3033
Abstract
CONTEXT Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. OBJECTIVE The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. METHODS Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample. RESULTS EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs. CONCLUSION Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.
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Lipid profile in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective lipid profile from single center.
Calapkulu, M, Cander, S, Gul, OO, Ersoy, C
Diabetes & metabolic syndrome. 2019;(2):1031-1034
Abstract
INTRODUCTION Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus which increasing urinary glucose excretion. With numerous controlled experimental studies of dapagliflozin, evaluation of real-life data after entry into clinical practice is an important condition. In our study, the effects of dapagliflozin (10 mg) on lipid profile were investigated retrospectively. METHODS A total of thirty-one type 2 diabetic patients with HbA1c level between 6,5% and 13%, aged 45-80 years and whose body mass index higher than 20 kg/m2 were enrolled to the study. Data before dapagliflozin treatment and three and six months results were recorded. RESULTS Dapagliflozin reduced HbA1c levels by 0,9% at 3 months and 0,79% at 6 months. Total cholesterol level decreased 17,6 mg/dl, LDL cholesterol level decreased 13,4 mg/dl and triglyceride level by 25.9 mg/dl at the 6th months and it is observed that there is no serious side effect on the usage for 6 months. CONCLUSION There are conflicting results about the effect of SGLT2 inhibitors on the lipid profile in the literature. According to our data, dapagliflozin has positive effects on lipid profile as weight and glycemic control and it is well tolerated. Therefore, dapagliflozin therapy is beneficial because of the positive change in lipid profile and weight loss in diabetic patients with overweight and hyperlipidemia.
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Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study.
Javed, Z, Papageorgiou, M, Deshmukh, H, Rigby, AS, Qamar, U, Abbas, J, Khan, AY, Kilpatrick, ES, Atkin, SL, Sathyapalan, T
Clinical endocrinology. 2019;(6):805-813
Abstract
BACKGROUND Empagliflozin is a sodium-glucose-cotransporter-2 inhibitor that improves cardiovascular risk and promotes weight loss in patients with type-2 diabetes. Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular risk; therefore, empagliflozin may be of benefit for these women. The aim of this study was to compare the effects of empagliflozin vs metformin on anthropometric and body composition, hormonal and metabolic parameters in women with PCOS. MATERIALS AND METHODS A randomized open-label study was conducted in women with PCOS who were randomized to either empagliflozin 25 mg (n = 19) or metformin 1500 mg (n = 20) daily for 12 weeks. The main outcomes assessed were changes in anthropometric and body composition, hormonal and metabolic parameters. RESULTS Univariate analysis showed significant differences in weight (empagliflozin: -1.4 ± 3.2% vs metformin: 1.2 ± 2.3%; P = 0.006), body mass index (empagliflozin: -1.4 ± 3.2% vs metformin: 1.1 ± 2.2%; P = 0.006), waist circumference (empagliflozin: -1.6 ± 2.8% vs metformin: 0.2 ± 2.1%; P = 0.029) and hip circumference (empagliflozin: -2.0 ± 3.0% vs metformin: 1.1 ± 1.9%; P = 0.001), basal metabolic rate (empagliflozin: -1.8 ± 2.9% vs metformin: 0.1 ± 1.9%, P = 0.024) and fat mass (empagliflozin: -0.7 ± 4.9% vs metformin, 3.2 ± 5.0%; P = 0.023) between the empagliflozin and the metformin groups. These differences were confirmed in linear regression analysis after adjustment for relevant covariates. There were no significant changes in hormonal or metabolic parameters between both groups. CONCLUSION There was a significant improvement in anthropometric parameters and body composition, in overweight and obese women with PCOS after 12 weeks of treatment with empagliflozin compared to metformin, although no changes were seen in hormonal or metabolic parameters.
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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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Anthropometric outcomes in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective glycemic control from single center.
Calapkulu, M, Cander, S, Gul, OO, Ersoy, C
Diabetes & metabolic syndrome. 2019;(1):284-288
Abstract
INTRODUCTION Dapagliflozin is an antidiabetic drug that has been used as a member of the new antidiabetic drug group that acts by inhibiting SGLT-2 and increasing urinary glucose excretion. With numerous controlled experimental studies of dapagliflozin, evaluation of real-life data after entry into clinical practice is an important condition. In our study, the effects of dapagliflozin on glycemic control and anthropometric measurements were investigated retrospectively. METHODS A-total of thirty-one type 2 diabetics were enrolled in the study. Data of before dapagliflozin and three and six months of treatment were recorded. RESULTS Dapagliflozin reduced HbA1c levels by 0,9% at 3 months and 0,79% at 6 months. Fasting plasma glucose decreased 41,1 mg/dl in the 3rd and 42 mg/dl in the 6th, postprandiyal glucose decreased 86,3 mg/dl in the 3rd and 74,2 mg/dl in the 6th. In the 3rd and 6th, body weights decreased by 3,3 kg and 4,2 kg, BMI decreased by 1,3 kg/m2 and 1,6 kg/m2 respectively. Similarly, it was observed that the waist circumference decreased by 1,3 cm at the end of 6th. CONCLUSION Our data show that SGLT-2 inhibitors provide glycemic control with reduce HbA1c levels by 0.8-0.9%, and reduce fasting and postprandial plasma glucose levels without increasing the risk of hypoglycemia and causing weight lose around 5% at the six mounths. SGLT-2 inhibitors were found to be more effective in reduce postprandiyal plasma glucose in patients who did not use insulin and fasting plasma glucose in patients with diabetes mellitus less than 10 years.
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Dapagliflozin: potential beneficial effects in the prevention and treatment of renal and cardiovascular complications in patients with type 2 diabetes.
Fioretto, P, Avogaro, A
Expert opinion on pharmacotherapy. 2017;(5):517-527
Abstract
Diabetic kidney disease is the leading cause of end-stage renal disease, a significant contributor to cardiovascular (CV) disease, responsible for much of the morbidity and mortality in patients with type 2 diabetes (T2DM). Strategies to slow or prevent the onset and progression of diabetic kidney disease are critical for effectively managing T2DM and reducing CV risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic agents, which may provide nephroprotective and CV protective effects. Areas covered: This review examines the role of the kidney in glucose homeostasis, discusses renal hemodynamic changes in diabetes, and outlines the major hypotheses regarding the mechanisms underlying renal injury in diabetes. The potential benefits of SGLT2 inhibitors in the prevention and treatment of CV complications in patients with T2DM are reviewed, with particular focus on dapagliflozin. Expert opinion: Dapagliflozin and other SGLT2 inhibitors have the capacity to decrease hyperglycemia and visceral fat, components of the metabolic syndrome particularly associated with the progression of CV disease. However, the mechanisms of action of SGLT2 inhibitors resulting in their positive CV effects remain unclear. Furthermore, the mechanism of action of SGLT2 inhibitors on heart function in non-diabetic patients with decompensated heart failure remains to be explored.
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[Potential sources of phthalates and bisphenol A and their significance in the development of metabolic diseases].
Mráz, M, Svačina, Š, Kotrlíková, E, Piecha, R, Vrbík, K, Pavloušková, J, Lacinová, Z, Vavrouš, A, Müllerová, D, Matějková, D, et al
Casopis lekaru ceskych. 2016;(3):11-5
Abstract
Nowadays, there is increasing evidence showing that the development of the metabolic syndrome combining obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia involves except of traditional risk factors (overnutrition, lack of physical activity, genetic predisposition) also the effect of environmental organic substances called organic pollutants or endocrine disruptors. These chemicals can be found in plastic covers, paints, flame retardants, exhaust gases, fertilizers as well as diverse daily utensils. Phthalates, used primarily as plasticizers, and bisphenol A, are among the most wide-spread members of this group.The aim of this article is to provide a basic overview of the relationship between phthalates and bisphenol A and the etiopathogenesis of the metabolic syndrome and to highlight their potential sources. According to the analysis of materials used for parenteral nutrition and urinary excretion of phthalate metabolites and bisphenol A in subjects on long-term parenteral nutrition we suppose that currently used medical materials are safe with respect to the exposure to both phthalates and bisphenol A and that home environment, especially cosmetic products, might constitute a more probable source of these substances.
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Bisphenol A: Targeting metabolic tissues.
Chevalier, N, Fénichel, P
Reviews in endocrine & metabolic disorders. 2015;(4):299-309
Abstract
The prevalence of obesity, metabolic syndrome and type 2 diabetes has dramatically increased worldwide over the last few decades. Although genetic predisposition and lifestyle factors like decreased physical activity and energy-dense diet are well-known factors in the pathophysiology of these conditions, accumulating evidence suggests that the increase in endocrine disrupting chemicals (EDCs) in the environment also explains a substantial part of the incidence of these metabolic diseases. Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide. Most people are exposed to it daily by consuming food and beverages into which BPA has leached from polycarbonate containers, including reusable bottles and baby bottles. Although initially considered to be a weak environmental estrogen, BPA may be similar in potency to 17β-estradiol in stimulating cellular responses, especially at low but environmentally relevant doses (nM), as more recent studies have demonstrated. In this review, we summarize both epidemiological evidence and in vivo experimental data that point to an association between BPA exposure and the induction of insulin resistance and/or disruption of pancreatic beta cell function and/or obesity. We then discuss the in vitro data and explain the potential mechanisms involved in the metabolic disorders observed after BPA exposure.