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https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/29251018/cardiovascular-outcomes-with-canagliflozin-is-it-on-the-canvas
#13
Sheila Doggrell
Sodium-glucose cotransporter 2 (SGLT2) inhibitors (the 'gliflozins') promote the excretion of glucose from the kidney to lower HbA1c. Empagliflozin was the first gliflozin shown to improve cardiovascular and renal outcomes in subjects with type 2 diabetes and cardiovascular disease. Areas covered: In the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, there were improvements in the primary cardiovascular and exploratory renal outcomes with canagliflozin, compared to placebo. The safety outcome finding, which was of most interest, was that there was a higher risk of amputation of toes, feet, or legs with canagliflozin than in the placebo group...
December 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29247356/current-and-future-pharmacological-therapies-for-nafld-nash
#14
REVIEW
Yoshio Sumida, Masashi Yoneda
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation...
December 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29216560/identification-of-an-oxime-containing-c-glucosylarene-as-a-potential-inhibitor-of-sodium-dependent-glucose-co-transporter-2
#15
Mao-Chia Yuan, Teng-Kuang Yeh, Chiung-Tong Chen, Jen-Shin Song, Yu-Chen Huang, Tsung-Chih Hsieh, Chung-Yu Huang, Yu-Ling Huang, Min-Hsien Wang, Szu-Huei Wu, Chun-Hsu Yao, Yu-Sheng Chao, Jinq-Chyi Lee
Treatment of hyperglycemia with drugs that block renal glucose reabsorption via inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel approach to diabetes management. In this study, twenty-seven aryl C-glycosides bearing a C=N/C-N linkage at the glucosyl C6 position were designed, synthesized and evaluated for their inhibitory activity against human SGLT2 (hSGLT2). Compounds with good hSGLT2 inhibition were further investigated to determine their selectivity over hSGLT1. Of these, five representative aryl C-glycosides were chosen for pharmacokinetic analysis...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29215196/comparison-between-sglt2-inhibitors-and-pioglitazone-as-additions-to-insulin-therapy-in-type-2-diabetes-a-systematic-review-with-an-indirect-comparison-meta-analysis
#16
Yun Kyung Cho, Ye-Jee Kim, Yu Mi Kang, Seung Eun Lee, Joong-Yeol Park, Woo Je Lee, Chang Hee Jung
AIMS/INTRODUCTION: We aimed to evaluate the efficacy and safety of pioglitazone (PIO) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) as additions to insulin therapy for the management of type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials. gov through December 2016. Randomized controlled trials (RCTs) published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus insulin (PIO/INS) with placebo plus insulin (PCB/INS) in T2D patients were included...
December 7, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29213337/effectiveness-of-long-term-treatment-with-sglt2-inhibitors-real-world-evidence-from-a-specialized-diabetes-center
#17
Yotsapon Thewjitcharoen, Nalin Yenseung, Areeya Malidaeng, Soontaree Nakasatien, Phawinpon Chotwanvirat, Sirinate Krittiyawong, Ekgaluck Wanothayaroj, Thep Himathongkam
Background: Diabetes is a progressive disease needing multiple drugs for achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several beneficial effects. However, the long-term effectiveness in clinical practice and safety data of SGLT2 inhibitors is limited, especially in Asian patients. To better understand the effectiveness of SGLT2i in clinical practice, we conducted a retrospective evaluation of patients with diabetes on SGLT2i...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29212386/efficacy-and-safety-of-sotagliflozin-in-treating-diabetes-type-1
#18
Marc S Rendell
INTRODUCTION: Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other agents as a result of decreased glucose absorption. The primary development effort to date has been in Type 1 diabetes. AREAS COVERED: The published information on sotagliflozin is reviewed, along with the recent results of several pivotal Type 1 diabetes trials...
December 7, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29211300/fluorine-directed-glycosylation-enables-the-stereocontrolled-synthesis-of-selective-sglt2-inhibitors-for-type-ii-diabetes
#19
Anna Sadurní, Gerald Kehr, Marie Ahlqvist, Helena Peilot Sjögren, Cecilia Kankkonen, Laurent Knerr, Ryan Gilmour
Inhibition of the sodium-glucose co-transporters (SGLT1 and SGLT2) is a validated strategy to address the increasing prevalence of type II diabetes mellitus. However, achieving selective inhibition of human SGLT1 or SGLT2 remains challenging. Orally available small molecule drugs based on the D-glucose core of the natural product Gliflozin have proven to be clinically effective in this regard, effectively impeding glucose reabsorption. Herein, we disclose the influence of molecular editing with fluorine at the C2 position of the pyranose ring of Phlorizin analogues Remogliflozin Etabonate and Dapagliflozin (Farxiga®) to concurrently direct β-selective glycosylation, as is required for biological efficacy, and enhance aspects of the physicochemical profile...
December 6, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29205334/sodium-glucose-cotransporter-2-inhibitor-canagliflozin-attenuates-liver-cancer-cell-growth-and-angiogenic-activity-by-inhibiting-glucose-uptake
#20
Kosuke Kaji, Norihisa Nishimura, Kenichiro Seki, Shinya Sato, Soichiro Saikawa, Keisuke Nakanishi, Masanori Furukawa, Hideto Kawaratani, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Hitoshi Yoshiji
Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2-Is to attenuate cancer growth of SGLT2-expressing cancer cells, little is known about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells...
December 4, 2017: International Journal of Cancer. Journal International du Cancer
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