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Sodium glucose transport inhibitors

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https://www.readbyqxmd.com/read/29039237/sglt2-inhibitors-are-they-safe
#1
Sebastian Filippas-Ntekouan, Theodosios D Filippatos, Moses S Elisaf
Sodium-glucose linked transporter type 2 (SGLT2) inhibitors are a relatively new class of anti-diabetic drugs with positive cardiovascular and kidney effects. The aim of this review is to present the safety issues associated with SGLT2 inhibitors. Urogenital infections are the most frequently encountered adverse events, although tend to be mild to moderate and are easily manageable with standard treatment. Although no increased acute kidney injury risk was evident in the major trials, the mechanism of action of these drugs requires caution when they are administered in patients with extracellular volume depletion or with drugs affecting renal hemodynamics...
October 17, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/29034006/canagliflozin-reduces-epicardial-fat-in-patients-with-type-2-diabetes-mellitus
#2
Shusuke Yagi, Yukina Hirata, Takayuki Ise, Kenya Kusunose, Hirotsugu Yamada, Daiju Fukuda, Hotimah Masdan Salim, Gulinu Maimaituxun, Susumu Nishio, Yuriko Takagawa, Saori Hama, Tomomi Matsuura, Koji Yamaguchi, Takeshi Tobiume, Takeshi Soeki, Tetsuzo Wakatsuki, Ken-Ichi Aihara, Masashi Akaike, Michio Shimabukuro, Masataka Sata
BACKGROUND: It is unknown whether canagliflozin, a selective sodium glucose co-transporter 2 inhibitor, reduces epicardial adipose tissue (EAT) thickness, which is associated with insulin resistance and is a risk factor for coronary artery disease. METHODS AND RESULTS: We administered 100 mg of canagliflozin for 6 months to 13 patients with type 2 diabetes mellitus. We evaluated glycemic control, visceral adipose tissue (VAT) area and subcutaneous adipose tissue (SAT) area, and skeletal muscle mass by using impedance methods, and EAT thickness by using echocardiography...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29032638/sodium-glucose-co-transporter-2-inhibitor-tofogliflozin-shows-better-improvements-of-blood-glucose-and-insulin-secretion-in-patients-with-high-insulin-levels-at-baseline
#3
Kazuyuki Tobe, Hideki Suganami, Kohei Kaku
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of drugs for the treatment of type 2 diabetes mellitus that improve control of plasma glucose and body weight, giving great hope for the clinical utility of these agents. However, it is unclear for which patients that SGLT2 inhibitors will be useful. MATERIALS AND METHODS: We analyzed data from long-term tofogliflozin monotherapy in an open-label, randomized controlled trial in Japanese patients with type 2 diabetes mellitus...
October 15, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29021363/novel-and-unexpected-functions-of-sglts
#4
REVIEW
Ernest M Wright, Chiara Ghezzi, Donald D F Loo
It has been 30 years since the intestinal sodium glucose cotransporter SGLT1 was cloned, and, in the intervening years, there have been many advances that have influenced physiology and medicine. Among the first was that SGLT1 is the founding member of the human gene family SLC5, containing 11 diverse transporters and a glucose sensor. Equally surprising was that SGLTs are members of a structural family of cotransporters and exchangers in different gene families. This led to the conclusion that these proteins operate by a mechanism where transport involves the opening and closing of external and internal gates...
November 2017: Physiology
https://www.readbyqxmd.com/read/28980272/pathogenesis-clinical-features-and-treatment-of-diabetic-cardiomyopathy
#5
Núria Alonso, Pedro Moliner, Dídac Mauricio
Patients with type 1 and type 2 diabetes mellitus (T1D and T2D) show an increased incidence of heart failure (HF) even after adjustment for well established risk factors for HF such as hypertension and ischaemic heart disease. The resulting specific form of cardiomyopathy is known as diabetic cardiomyopathy" (DCM). Pathogenetic mechanisms underlying DCM are likely to be multifactorial, from altered myocardial metabolism (hyperglycaemia, hyperinsulinaemia, increased circulating fatty acids and trglycerides) to microvascular disease, autonomic neuropathy, and altered myocardial structure with fibrosis...
October 5, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28976221/dapagliflozin-attenuates-human-vascular-endothelial-cell-activation-and-induces-vasorelaxation-a-potential-mechanism-for-inhibition-of-atherogenesis
#6
Tracey Gaspari, Iressa Spizzo, HongBin Liu, Yunshan Hu, Richard W Simpson, Robert E Widdop, Anthony E Dear
BACKGROUND: Sodium glucose transporter type 2 inhibitors may reduce cardiovascular events in type 2 diabetes. Our study aimed to determine the effect of the sodium glucose transporter type 2 inhibitor dapagliflozin on endothelial cell activation, vasoreactivity and atherogenesis using in vitro and in vivo models and identify associated molecular mechanisms. METHODS: In vitro studies utilised human vascular endothelial cells stimulated with tumour necrosis factor α or hyperglycaemic conditions...
October 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28952138/can-sglt2-inhibitors-cause-acute-renal-failure-plausible-role-for-altered-glomerular-hemodynamics-and-medullary-hypoxia
#7
REVIEW
Auryan Szalat, Amichai Perlman, Mordechai Muszkat, Mogher Khamaisi, Zaid Abassi, Samuel N Heyman
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) provide outstanding long-term cardiovascular and renal protection in high-risk patients with type 2 diabetes mellitus. Yet, despite encouraging renal safety outcomes reported in the EMPA-REG study, scattered reports suggest that there might be a risk for acute kidney injury (AKI), which may occasionally be fatal or might require renal replacement therapy. Reduced trans-glomerular pressure with a modest decline in kidney function, an inherent characteristic of SGLT2i therapy, conceivably forms the basis for the long-term renal protection, resembling agents that block the renin-angiotensin-aldosterone (RAAS) axis...
September 26, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28948541/cost-of-glycemic-target-achievement-with-sodium-glucose-co-transporter-2-inhibitors-in-patients-with-type-2-diabetes-in-the-uk
#8
Marc Evans, Sayeed Achha, Cheryl Neslusan
INTRODUCTION: Diabetes-related costs make up a large portion of healthcare expenditures in the UK. Many of these costs are related to treatment of diabetes-related complications. Reducing HbA1c to <7.0% (53 mmol/mol) reduces the incidence of complications and comorbidities. Metformin plus sulfonylurea is the most common dual oral combination therapy in the UK. The costs of achieving HbA1c <7.0% in patients inadequately controlled on metformin plus sulfonylurea were analyzed for the sodium glucose co-transporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin from the perspective of the UK National Health System...
September 25, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28934557/a-safety-evaluation-of-empagliflozin-plus-linagliptin-for-treating-type-2-diabetes
#9
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/28924948/magnetic-nanoparticles-for-the-delivery-of-dapagliflozin-to-hypoxic-tumors-physicochemical-characterization-and-cell-studies
#10
Athina Angelopoulou, Efstathia Voulgari, Argiris Kolokithas-Ntoukas, Aristides Bakandritsos, Konstantinos Avgoustakis
In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors...
September 18, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28911306/management-of-blood-pressure-and-heart-rate-in-patients-with-diabetes-mellitus
#11
Ioanna Gouni-Berthold, Ruth Hanssen, Lisa Ravarani, Heiner K Berthold
BACKGROUND: In patients with diabetes mellitus (DM) there is a clear association between blood pressure (BP) levels and macrovascular and microvascular complications. However, the BP targets that need to be achieved for optimal outcomes remain controversial. METHODS: The purpose of this narrative review is to discuss BP targets and management in patients with DM. The subject of elevated heart rate, which has been associated with mortality in many populations, and which is observed in some patients with DM will also be addressed...
June 8, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28898514/risk-of-lower-extremity-amputations-in-people-with-type-2-diabetes-mellitus-treated-with-sodium-glucose-co-transporter-2-inhibitors-in-the-usa-a-retrospective-cohort-study
#12
Zhong Yuan, Frank J DeFalco, Patrick B Ryan, Martijn J Schuemie, Paul E Stang, Jesse A Berlin, Mehul Desai, Norm Rosenthal
AIMS: To examine the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co-transporter 2 (SGLT2) inhibitors overall, and canagliflozin specifically, compared with non-SGLT2 inhibitor antihyperglycaemic agents (AHAs). MATERIALS AND METHODS: Patients with T2DM newly exposed to SGLT2 inhibitors or non-SGLT2 inhibitor AHAs were identified using the Truven MarketScan database. The incidence of below-knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2 inhibitors, canagliflozin, or non-SGLT2 inhibitor AHAs...
September 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#13
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#14
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/28887847/fournier-s-gangrene-in-a-man-on-empagliflozin-for-treatment-of-type-2-diabetes
#15
S Kumar, A J Costello, P G Colman
Use of sodium glucose co-transporter 2 (SLGT2) inhibitors has been associated with an increased risk of genital infections secondary to increased glycosuria [1]. Our report highlights a case of Fournier's gangrene, the most severe and potentially fatal type of genital infection, which was preceded by multiple episodes of thrush in a man treated with empagliflozin for Type 2 diabetes. This article is protected by copyright. All rights reserved.
September 8, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28870145/real-world-use-and-modeled-impact-of-glucose-lowering-therapies-evaluated-in-recent-cardiovascular-outcomes-trials-an-ncdr%C3%A2-research-to-practice-project
#16
Suzanne V Arnold, Silvio E Inzucchi, Fengming Tang, Darren K McGuire, Sanjeev N Mehta, Thomas M Maddox, Abhinav Goyal, Laurence S Sperling, Daniel Einhorn, Nathan D Wong, Kamlesh Khunti, Carolyn Sp Lam, Mikhail Kosiborod
Aims Recent trials (EMPA-REG OUTCOME and Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]) have shown improved cardiovascular (CV) mortality with specific currently available glucose-lowering medications (empagliflozin and liraglutide, respectively), but were limited to selected patient populations. We sought to evaluate the current use and potential real-world impact of empagliflozin (and other sodium-glucose co-transporter 2 inhibitors [SGLT2is]) and liraglutide (and other glucagonlike peptide-1 receptor agonist [GLP-1 RAs]) among patients in the Diabetes Collaborative Registry (DCR)...
October 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28864997/rationale-design-and-baseline-characteristics-of-the-utopia-trial-for-preventing-diabetic-atherosclerosis-using-an-sglt2-inhibitor-a-prospective-randomized-open-label-parallel-group-comparative-study
#17
Naoto Katakami, Tomoya Mita, Hidenori Yoshii, Toshihiko Shiraiwa, Tetsuyuki Yasuda, Yosuke Okada, Yutaka Umayahara, Hideaki Kaneto, Takeshi Osonoi, Tsunehiko Yamamoto, Nobuichi Kuribayashi, Kazuhisa Maeda, Hiroki Yokoyama, Keisuke Kosugi, Kentaro Ohtoshi, Isao Hayashi, Satoru Sumitani, Mamiko Tsugawa, Makoto Ohashi, Hideki Taki, Tadashi Nakamura, Satoshi Kawashima, Yasunori Sato, Hirotaka Watada, Iichiro Shimomura
INTRODUCTION: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are anti-diabetic agents that improve glycemic control with a low risk of hypoglycemia and ameliorate a variety of cardiovascular risk factors. The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker...
September 1, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28864828/-severe-atypical-ketoacidosis-due-to-sglt2-inhibitor-therapy-two-case-reports
#18
T G K Breuer, K Kampmann, A Wutzler, C Steinfort, W Uhl, W E Schmidt, J J Meier
Two female patients were admitted due to ketoacidosis. Serum glucose was moderately elevated. The patients exhibited abdominal and neurologic symptoms. Treatment consisted of metformin, insulin glargin and empagliflozin, as well as glimepiride, insulin detemir and empagliflozin, respectively. Treatment with intravenous fluid replacement, insulin, glucose, potassium and buffer solution led to a normalisation of pH and serum glucose levels. Our report describes two cases of atypical ketoacidosis with moderately elevated serum glucose during sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy...
September 1, 2017: Der Internist
https://www.readbyqxmd.com/read/28858200/sympathomodulatory-effects-of-sodium-glucose-transporter-2-inhibitors-in-the-kidneys-and-beyond
#19
Peter J Blankestijn, Christoph Wanner, Guido Grassi
No abstract text is available yet for this article.
October 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28846182/effects-of-sodium-glucose-co-transporter-2-sglt2-inhibitors-on-serum-uric-acid-level-a-meta-analysis-of-randomized-controlled-trials
#20
Yumo Zhao, Lubin Xu, Dongli Tian, Peng Xia, Hua Zheng, Li Wang, Limeng Chen
To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM), PubMed, CENTRAL, EMBASE, and ClinicalTrials.gov were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to 20 May 2017. Sixty-two studies totaling 34,941 patients were included. Either SGLT2 inhibitor (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total WMD -37...
August 28, 2017: Diabetes, Obesity & Metabolism
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