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https://www.readbyqxmd.com/read/29353233/cardiovascular-safety-long-term-noncardiovascular-safety-and-efficacy-of-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-type-2-diabetes-mellitus-a-systemic-review-and-meta-analysis-with-trial-sequential-analysis
#1
REVIEW
Xin-Lin Zhang, Qing-Qing Zhu, Yu-Han Chen, Xue-Ling Li, Fu Chen, Jian-An Huang, Biao Xu
BACKGROUND: The cardiovascular and long-term noncardiovascular safety and efficacy of SGLT2 (sodium-glucose cotransporter 2) inhibitors have not been well documented. METHODS AND RESULTS: For cardiovascular outcomes, we performed a meta-analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient-years of follow-up. For long-term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient-years of follow-up...
January 20, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29352520/ipragliflozin-improves-mitochondrial-abnormalities-in-renal-tubules-induced-by-a-high-fat-diet
#2
Susumu Takagi, Jinpeng Li, Yuta Takagaki, Munehiro Kitada, Kyoko Nitta, Toshiyuki Takasu, Keizo Kanasaki, Daisuke Koya
OBJECTIVE: Complete mechanisms of reno-protective effects of SGLT2 inhibitors have not been elucidated yet. Mitochondrial biogenesis is regulated by membrane GTPases, such as Opa1 and Mfn2. Here, we investigated whether SGLT2 inhibition in mice fed with a high-fat diet (HFD) improved mitochondrial morphology and restored mitochondrial biogenesis-related molecules. MATERIALS AND METHODS: Mice were fed in control diet or HFD with or without ipragliflozin treatment...
January 20, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29349558/sglt2-inhibitors-and-mechanisms-of-hypertension
#3
REVIEW
Alexandros Briasoulis, Omar Al Dhaybi, George L Bakris
PURPOSE OF REVIEW: We sought to review currently available data on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes mellitus patients with hypertension. RECENT FINDINGS: Inhibition of SGLT2 in the renal proximal tubule results in increased urinary glucose excretion and modest improvements of hemoglobin A1C. Treatment with any of the three currently FDA-approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results in sustained systolic and diastolic blood pressure reduction, in part via minimal natriuresis and possible reductions in sympathetic tone...
January 19, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29344329/major-adverse-cardiovascular-event-reduction-with-glp-1-and-sglt2-agents-evidence-and-clinical-potential
#4
REVIEW
Michael E Røder
Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29342295/empagliflozin-treatment-is-associated-with-improved-beta-cell-function-in-t2dm
#5
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Carolina Solis-Herrera, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
Objective: To examine whether lowering the plasma glucose concentration with empagliflozin (SGLT2 inhibitor) improves beta cell function in T2DM. Research Design and Methods: 15 T2DM patients received empagliflozin (25 mg/day) for 2 weeks, and beta cell function was measured with 9-step hyperglycemic clamp (each step = +40 mg/dl) before and 48 hours and 14 days after empagliflozin. Results: Empagliflozin caused 101±10 and 117±11 grams glucosuria on days 1 and 14 and produced 25±6 and 38±8 mg/dl reduction (p<0...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29341526/-the-internal-medicine-articles-that-struck-us-the-most-in-2017
#6
Vanessa Kraege, Evrim Jaccard, Alain Kenfak, Elisabeth Stamm, Fanny Blondet, Grégoire Humair, Plamena Tasheva, Oriane Aebischer, Sabine Giroud, Jonathan Tschopp, Claudio Sartori
2017 has continued to bring important progress in all areas of internal medicine, impacting our daily practice. From bedside screening for beta-lactam allergies, to statins as primary prevention in the elderly, SGLT2 inhibitors in heart failure, azithromycin in severe asthmatics and tofacitinib in ulcero-haemorrhagic recto-colitis, internal medicine journals are full of novelties. Every year, the chief residents of the CHUV internal medicine ward meet up to share their readings: here is their selection of eleven articles, chosen, summarized and commented for you...
January 17, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29341404/intra-and-inter-subject-variability-for-increases-in-serum-ketone-bodies-in-patients-with-type-2-diabetes-treated-with-the-sodium-glucose-co-transporter-2-inhibitor-canagliflozin
#7
David Polidori, Hiroaki Iijima, Maki Goda, Nobuko Maruyama, Nobuya Inagaki, Peter A Crawford
SGLT2 inhibitors have been associated with increased serum ketone bodies in patients with type 2 diabetes mellitus (T2DM). This analysis evaluated serum ketone body levels and variability in 1,278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen with both canagliflozin doses. Median (interquartile range) percent change from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for β-hydroxybutyrate. Approximately 2/3 of the variability in each ketone measure was attributed to intra-subject variability...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29335890/effectiveness-of-sodium-glucose-cotransporter-2-inhibitor-as-an-add-on-drug-to-glp-1-receptor-agonists-for-glycemic-control-of-a-patient-with-prader-willi-syndrome-a-case-report
#8
Yukio Horikawa, Mayumi Enya, Makie Komagata, Ken-Ichi Hashimoto, Masayo Kagami, Maki Fukami, Jun Takeda
INTRODUCTION: Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS. CASE REPORT: A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age. At age 16 years, he was diagnosed with diabetes and began to take several kinds of oral hypoglycemic agents...
January 15, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#9
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29330646/potential-impact-of-sglt2-inhibitors-on-left-ventricular-diastolic-function-in-patients-with-diabetes-mellitus
#10
REVIEW
Hidekazu Tanaka, Ken-Ichi Hirata
The pathogenesis of diabetes mellitus (DM)-related cardiac dysfunction is thought to be multifactorial, and possibly a key factor for the development of heart failure with preserved ejection fraction (HFpEF) in patients with DM and preserved left ventricular (LV) ejection fraction. Currently, there is no effective treatment for HFpEF, which is presented as LV diastolic dysfunction. Furthermore, it is well known that, in addition to DM, hypertension and overweight/obesity are also important factors associated with HFpEF...
January 12, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29322280/direct-cardiovascular-impact-of-sglt2-inhibitors-mechanisms-and-effects
#11
REVIEW
Abdullah Kaplan, Emna Abidi, Ahmed El-Yazbi, Ali Eid, George W Booz, Fouad A Zouein
Diabetes is a global epidemic and a leading cause of death with more than 422 million patients worldwide out of whom around 392 million alone suffer from type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel and effective drugs in managing glycemia of T2D patients. These inhibitors gained recent clinical and basic research attention due to their clinically observed cardiovascular protective effects. Although interest in the study of various SGLT isoforms and the effect of their inhibition on cardiovascular function extends over the past 20 years, an explanation of the effects observed clinically based on available experimental data is not forthcoming...
January 11, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29320602/when-metformin-is-not-enough-pros-and-cons-of-sglt2-and-dpp-4-inhibitors-as-a-second-line-therapy
#12
REVIEW
Angelo Avogaro, Elías Delgado, Ildiko Lingvay
The newer oral therapies for type 2 diabetes (T2DM); dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have advantages over older agents. DPP-4 inhibitors are weight neutral, and have few adverse effects. SGLT2 inhibitors have additional benefits; weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. SGLT2 inhibitors, have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis...
January 10, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29317332/safety-and-efficacy-of-sodium-glucose-cotransporter-2-sglt2-inhibitors-in-type-1-diabetes-a-systematic-review-and-meta-analysis
#13
REVIEW
Dana El Masri, Samiran Ghosh, Linda A Jaber
AIMS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are currently FDA approved for the management of type 2 diabetes. Our objective was to review the available evidence of the effects of SGLT2 inhibitors on HbA1c, body weight, and total daily insulin dose, as well as their safety profile in patients with type 1 diabetes. METHODS: Four randomized controlled trials (RCTs) were identified by conducting a systematic search of PubMed, Embase, Web of Science, Scopus and Cochrane library databases through August 2017...
January 6, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29307883/phlorizin-exerts-direct-protective-effects-on-palmitic-acid-pa-induced-endothelial-dysfunction-by-activating-the-pi3k-akt-enos-signaling-pathway-and-increasing-the-levels-of-nitric-oxide-no
#14
Chun-Ying Li, Liang-Xue Wang, Si-Si Dong, Ying Hong, Xin-He Zhou, Wen-Wen Zheng, Chao Zheng
BACKGROUND Sodium glucose transporter-2 inhibitors are the newest antidiabetic drugs that seem to be cardioprotective and can prevent type 2 diabetes in patients with high cardiovascular risks. Previous clinical trials have shown that these inhibitors can alleviate endothelial dysfunction, but the mechanism of action remains unknown. How SGLT inhibitor influences the release of NO in PA-induced HUVECs has never been reported. MATERIAL AND METHODS To explore the potential effects of the endothelial-protective mechanism of phlorizin and its impact on nitric oxide (NO), human umbilical vein endothelial cells (HUVECs) were incubated with palmitic acid (PA) and then treated with phlorizin...
January 8, 2018: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/29306791/empagliflozin-rescues-diabetic-myocardial-microvascular-injury-via-ampk-mediated-inhibition-of-mitochondrial-fission
#15
Hao Zhou, Shuyi Wang, Pingjun Zhu, Shunying Hu, Yundai Chen, Jun Ren
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29302934/a-class-comparison-of-medication-persistence-in-people-with-type-2-diabetes-a-retrospective-observational-study
#16
Andrew McGovern, William Hinton, Silvio Calderara, Neil Munro, Martin Whyte, Simon de Lusignan
INTRODUCTION: Longer medication persistence in type 2 diabetes (T2D) is associated with improved glycaemic control. It is not clear which oral therapies have the best persistence. The objective of this study was to compare medication persistence across different oral therapies in people with T2D. METHODS: We performed a retrospective cohort analysis using a primary-care-based population, the Royal College of General Practitioners Research and Surveillance Centre cohort...
January 4, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29301371/the-sodium-glucose-cotransporter-2-inhibitor-dapagliflozin-prevents-renal-and-liver-disease-in-western-diet-induced-obesity-mice
#17
Dong Wang, Yuhuan Luo, Xiaoxin Wang, David J Orlicky, Komuraiah Myakala, Pengyuan Yang, Moshe Levi
Obesity and obesity related kidney and liver disease have become more prevalent over the past few decades, especially in the western world. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with promising effects on cardiovascular and renal function. Given SGLT2 inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of the highly selective renal SGLT2 inhibitor dapagliflozin in mice with Western diet (WD) induced obesity...
January 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29285507/comparative-effectiveness-of-cardiovascular-outcomes-in-new-users-of-sodium-glucose-cotransporter-2-inhibitors-sglt2-inhibitors-in-the-real-world
#18
EDITORIAL
Richard J MacIsaac, Elif I Ekinci
No abstract text is available yet for this article.
December 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29285488/comparative-effectiveness-and-safety-of-empagliflozin-on-cardiovascular-mortality-and-morbidity-in-adults-with-type-2-diabetes
#19
Wilbert S Aronow, Tatyana A Shamliyan
Background: Based on a single placebo-controlled randomized clinical trial, empagliflozin is licensed to reduce cardiovascular death in diabetes and comorbid cardiovascular disease. Methods: We examined the comparative effectiveness of empagliflozin on mortality and cardiovascular morbidity in type 2 diabetes. We conducted random-effects direct frequentist meta-analyses of aggregate data and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology...
December 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29251736/pge2-ep1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#20
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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