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SGLT-2 Inhibitors

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https://www.readbyqxmd.com/read/29144574/sglt-2-inhibitors-and-ketoacidosis-a-disproportionality-analysis-in-the-world-health-organization-s-adverse-drug-reactions-database
#1
Abdel Nasser Ado Moumouni, Perrine Robin, Dominique Hillaire-Buys, Jean-Luc Faillie
SGLT-2 inhibitors, also called gliflozins, are a new class of drugs used in type 2 diabetes. Since their marketing, several cases of ketoacidosis, including life-threatening conditions, were reported with their use. The objective of this study was to investigate the disproportionality of pharmacovigilance reports of ketoacidosis between gliflozins and other drugs used for type 2 diabetes. We performed a case non-case study within the World Health Organization's pharmacovigilance database, VigiBase. We selected all reports of serious adverse drug reaction associated with a glucose-lowering drug in patients aged 40 years and older, from January 2013 to March 2016...
November 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29133603/canagliflozin-cui-bono
#2
Matthew A Cavender, Mikhail Kosiborod
Cardiovascular disease accounts for the majority of excess deaths seen in patients with Type 2 diabetes (T2D).(1) Thus, in order to improve outcomes in this population, clinicians should focus on therapies that decrease the risk of subsequent cardiovascular events. Over the last two years, randomized controlled clinical trials have identified several agents that decrease cardiovascular events in patients with T2D with or at high risk for cardiovascular disease (CVD) - effects likely unrelated to glucose-lowering, the indication for which they were originally developed...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29127652/dapagliflozin-as-a-cause-of-acute-tubular-necrosis-with-heavy-consequences-a-case-report
#3
Christos Pleros, Elisavet Stamataki, Antonia Papadaki, Nikolaos Damianakis, Rafaela Poulidaki, Charikleia Gakiopoulou, Ioannis Tzanakis
A 50-year-old man with type II diabetes, hypertension and dyslipidemia, presented with non-oliguric acute kidney injury (AKI) and anemia. Renal biopsy showed acute tubular necrosis (ATN) with extensive cytoplasmic vacuolization and areas of tubulitis. These findings were ultimately attributed to dapagliflozin, which he started 3 months earlier due to poor glycemic control. ATN with similar microscopic findings has been described with larger doses of dapagliflozin in non-clinical trials. Our patient was started on dialysis and remained dialysis-dependent for 4 weeks while his renal function improved gradually thereafter...
November 10, 2017: CEN Case Reports
https://www.readbyqxmd.com/read/29126986/functional-redundancy-of-glucose-acquisition-mechanisms-in-the-hindgut-of-pacific-hagfish-eptatretus-stoutii
#4
Alyssa M Weinrauch, Alexander M Clifford, Greg G Goss
This study examined the mechanisms of glucose acquisition in the hindgut of Pacific hagfish (Eptatretus stoutii) using in vitro gut sac techniques. The intestine was determined to have the capacity to digest maltose into glucose along the entirety of the tract, including the foregut. Glucose uptake was biphasic and consisted of a high-affinity, low-capacity concentration-dependent component conforming to Michaelis-Menten kinetics (Km 0.37mM, Jmax 8.48nmol/cm(2)/h) as well as a diffusive component. There was no observed difference in glucose flux rate along the length of the intestine, similar to other nutrients investigated in the hagfish intestine...
November 7, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29077267/sglt-2-inhibitors-and-cardiovascular-outcome-studies-in-type-2-diabetes-from-efficacy-to-effectiveness
#5
K Khunti, M Kosiborod
Cardiovascular disease remains the main cause of morbidity and mortality in people with diabetes, and is also the largest contributor to healthcare costs in this population(1).
October 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29076038/long-term-effectiveness-of-liraglutide-in-association-with-patients-baseline-characteristics-in-real-life-setting-in-croatia-an-observational-retrospective-multicenter-study
#6
Maja Cigrovski Berkovic, Ines Bilic-Curcic, Davorka Herman Mahecic, Marina Gradiser, Mladen Grgurevic, Tomislav Bozek
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are recommended therapy for type 2 diabetes (T2DM) and liraglutide is the most used worldwide. We assessed the glycemic efficacy and extra-glycemic effects of liraglutide during 36 months' follow-up of individuals with poorly regulated T2DM under routine clinical practice and sought to identify the phenotype of treatment responders. METHODS: A total of 207 individuals were included. The primary endpoint was the proportion of participants with HbA1c < 7...
December 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29074013/newer-classes-of-antidiabetes-drugs-ophthalmological-considerations-for-glp-1r-agonists-dpp-4-inhibitors-and-sglt-2-inhibitors
#7
EDITORIAL
Kylen D McReelis, Julie A Lovshin
No abstract text is available yet for this article.
November 2017: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/29052845/the-advanced-glycation-end-product-n-%C3%AF%C2%B5-carboxymethyllysine-and-its-precursor-glyoxal-increase-serotonin-release-from-caco-2-cells
#8
Ann-Katrin Holik, Barbara Lieder, Nicole Kretschy, Mark M Somoza, Jakob P Ley, Joachim Hans, Veronika Somoza
Advanced glycation end products (AGEs), comprising a highly diverse class of Maillard reaction compounds formed in vivo and during heating processes of foods, have been described in the progression of several degenerative conditions such as Alzheimer's disease and diabetes mellitus. N(ϵ) -Carboxymethyllysine (CML) represents a well-characterized AGE, which is frequently encountered in a Western diet and is known to mediate its cellular effects through binding to the receptor for AGEs (RAGE). Since very little is known about the impact of exogenous CML and its precursor, glyoxal, on intestinal cells, a genome-wide screening using a customized microarray was conducted in fully differentiated Caco-2 cells...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29047219/addition-of-dipeptidyl-peptidase-4-inhibitors-to-insulin-treatment-in-type-2-diabetes-patients-a-meta-analysis
#9
Wenjia Yang, Xiaoling Cai, Xueying Gao, Yifei Chen, Chen Ling, Linong Ji
AIMS: To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase 4 (DPP-4) inhibitors compared to combining insulin therapy with placebo or other antihyperglycaemic agents. MATERIALS AND METHODS: A literature search was conducted via electronic databases. The inclusion criteria were randomized controlled trials (RCTs) comparing the addition of DPP-4 inhibitors to insulin with the addition of placebo or other active hypoglycaemic agents to insulin therapy, study duration of no less than 12 weeks performed in type 2 diabetes patients, and the availability of outcome data to evaluate a change in the HbA1c ...
October 19, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29020969/updates-on-cardiovascular-outcome-trials-in-diabetes
#10
REVIEW
Oliver Schnell, Lars Rydén, Eberhard Standl, Antonio Ceriello
In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications. Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk...
October 11, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28977090/use-of-sglt-2-inhibitors-in-the-treatment-of-type-2-diabetes-mellitus
#11
REVIEW
Leyna Leite Santos, Fernando José Camello de Lima, Célio Fernando de Sousa-Rodrigues, Fabiano Timbó Barbosa
INTRODUCTION: Diabetes mellitus is one of the most common chronic diseases in the world, with high morbidity and mortality rates, resulting in a greatly negative socioeconomic impact. Although there are several classes of oral antidiabetic agents, most of the patients are outside the therapeutic goal range. OBJECTIVE: To review the use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus, focusing on their favorable and unfavorable effects, as well as on cardiovascular profile...
July 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28934557/a-safety-evaluation-of-empagliflozin-plus-linagliptin-for-treating-type-2-diabetes
#12
Baptist Gallwitz
Dipeptidyl-peptidase-IV inhibitors (DPP-4i) and sodium-glucose-transporter-2 inhibitors (SGLT-2i) are oral antidiabetic drugs that improve glycemic parameters and possess a very low intrinsic hypoglycemia risk and favorable cardiovascular data. Areas covered: An overview on the clinical studies investigating the combination therapy with the DPP-4i linagliptin and the SGLT-2i empagliflozin is given. The clinical evidence for the efficacy and safety of free combinations as well as for their fixed dose combinations is presented...
October 11, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#13
REVIEW
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28872070/hydrogen-bonded-structures-and-interaction-energies-in-two-forms-of-the-sglt-2-inhibitor-sotagliflozin
#14
Thomas Gelbrich, Verena Adamer, Marijan Stefinovic, Andrea Thaler, Ulrich J Griesser
The sotagliflozin molecule exhibits two fundamentally different molecular conformations in form 1 {systematic name: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(methylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol, C21H25ClO5S, (I)} and the monohydrate [C21H25ClO5S·H2O, (II)]. Both crystals display hydrogen-bonded layers formed by intermolecular interactions which involve the three -OH groups of the xyloside fragment of the molecule. The layer architectures of (I) and (II) contain a non-hydrogen-bonded molecule-molecule interaction along the short crystallographic axis (a axis) whose total PIXEL energy exceeds that of each hydrogen-bonded molecule-molecule pair...
September 1, 2017: Acta Crystallographica. Section C, Structural Chemistry
https://www.readbyqxmd.com/read/28871349/recent-insights-into-pharmacologic-cardiovascular-risk-reduction-in-type-2-diabetes-mellitus
#15
Scott L Purga, Mandeep Sidhu, Michael Farkouh, Joshua Schulman-Marcus
Diabetes mellitus (DM) affects nearly 30 million Americans and carries an increased risk of macrovascular complications of myocardial infarction, stroke, and cardiovascular death. While aggressive cardiovascular risk factor reduction has long been advocated in patients with diabetes, clinical trials have only recently demonstrated that such reductions result in improved outcomes. This review discusses recent evidence for risk reduction strategies and therapies with a focus on the management of glycemia, dyslipidemia, and hypertension...
August 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28840014/cardiovascular-benefits-of-the-newer-medications-for-treating-type-2-diabetes-mellitus
#16
REVIEW
Srikanth Yandrapalli, Wilbert S Aronow
Diabetes mellitus is growing in pandemic proportions and is associated with significant morbidity, mortality, and health care expenditure. Type 2 diabetes mellitus (T2DM) is the most common, accounting for about 90-95% of diagnosed diabetes in United States adults. Individuals with T2DM have a 2- to 3-fold increased risk of cardiovascular (CV) events compared with their non-diabetic counterparts, and CV mortality is responsible for around 80% of the mortality in T2DM. Emerging evidence suggest that in T2DM patients, hyperglycemia plays a little role in the progression of CV disease, and metabolic risk factors like insulin resistance, hypertension, obesity, and dyslipidemia are the major culprits in the initiation and progression of CV disease...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28827404/acute-kidney-injury-in-patients-on-sglt2-inhibitors-a-propensity-matched-analysis
#17
Girish N Nadkarni, Rocco Ferrandino, Alexander Chang, Aditya Surapaneni, Kinsuk Chauhan, Priti Poojary, Aparna Saha, Bart Ferket, Morgan E Grams, Steven G Coca
OBJECTIVE: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D. RESEARCH DESIGN AND METHODS: We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort...
November 2017: Diabetes Care
https://www.readbyqxmd.com/read/28822958/therapeutic-molecules-against-type-2-diabetes-what-we-have-and-what-are-we-expecting
#18
REVIEW
Ashwini Kumar, Sudhanshu Kumar Bharti, Awanish Kumar
World Health Organization (WHO) has identified diabetes as one of the fastest growing non-communicable diseases with 422 million patients around the world in 2014. Diabetes, a metabolic disease, is characterized primarily by hyperglycemia which results in various macrovascular and microvascular complications like cardiovascular disease and neuropathies which can significantly deteriorate the quality of life. The body either does not manufactures enough insulin (type 1 diabetes or T1DM) or becomes insensitive to physiologically secreted insulin or both (type 2 diabetes or T2DM)...
April 9, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28797524/systematic-review-of-metformin-monotherapy-and-dual-therapy-with-sodium-glucose-co-transporter-2-inhibitor-sglt-2-in-treatment-of-type-2-diabetes-mellitus
#19
REVIEW
Nagashekhara Molugulu, Lai Shu Yee, Yew Tze Ye, Tan Chew Khee, Lee Zhen Nie, Neoh Jia Yee, Tian Kar Yee, Tan Chee Liang, Prashant Kesharwani
BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a chronic disorder and its treatment with only metformin often does not provide optimum glycemic control. Addition of sodium glucose cotransporter 2 inhibitor (SGLT2) will improve the glycemic control in patients on metformin alone. In this study, an attempt is made to investigate the combined therapy of SGLT-2 with metformin in managing T2DM in terms of lowering HbA1c and body weight and monotherapy using metformin alone in HbA1c and body weight reduction...
October 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28794821/comparing-medication-adherence-and-persistence-among-patients-with-type-2-diabetes-using-sodium-glucose-cotransporter-2-inhibitors-or-sulfonylureas
#20
Kelly F Bell, Katherine Cappell, Michael Liang, Amanda M Kong
BACKGROUND: Patients with type 2 diabetes treated with pharmacotherapy should be adherent to and persistent with their medications to experience glycemic control and prevent associated complications. OBJECTIVE: To compare medication adherence and persistence among patients with type 2 diabetes who are newly initiating a sodium-glucose cotransporter 2 (SGLT-2) inhibitor or a sulfonylurea. METHODS: This was a retrospective, observational cohort study using the MarketScan claims databases...
June 2017: American Health & Drug Benefits
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