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https://www.readbyqxmd.com/read/29790389/unmasking-a-sustained-negative-effect-of-sglt2-inhibition-on-body-fluid-volume-in-the-rat
#1
Takahiro Masuda, Yuko Watanabe, Keiko Fukuda, Minami Watanabe, Akira Onishi, Ken Ohara, Toshimi Imai, Hermann Koepsell, Shigeaki Muto, Volker Vallon, Daisuke Nagata
The chronic intrinsic diuretic and natriuretic tone of sodium-glucose cotransporter 2 (SGLT2) inhibitors is incompletely understood, because their effect on body fluid volume (BFV) has not been fully evaluated and because they often increase food and fluid intake at the same time. Here we first compared the effect of the SGLT2 inhibitor ipragliflozin (Ipra, 0.01% in diet for 8 weeks) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a non-obese type 2 diabetic model, and non-diabetic Sprague-Dawley rats...
May 23, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29788782/are-sglt2-inhibitors-or-glp-1-receptor-agonists-more-appropriate-as-a-second-line-therapy-in-type-2-diabetes
#2
Kashif M Munir, Stephen N Davis
No abstract text is available yet for this article.
May 22, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29783787/plasma-pharmacokinetic-determination-of-canagliflozin-and-its-metabolites-in-a-type-2-diabetic-rat-model-by-uplc-ms-ms
#3
Song-Tao Dong, Hui-Min Niu, Yin Wu, Jia-Lei Jiang, Ying Li, Kun-Yu Jiang, Xin Wang, Mao-Fan Zhang, Ming-Feng Han, Sheng-Nan Meng
Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a sensitive and efficient UPLC-MS/MS method for the quantification of canagliflozin and its metabolites in rat plasma was established and applied to pharmacokinetics in a type 2 diabetic rat model. We firstly investigated the pharmacokinetic changes of canagliflozin and its metabolites in type 2 diabetic rats in order to use canagliflozin more safely, reasonably and effectively...
May 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29766812/switching-dipeptidyl-peptidase-4-inhibitors-to-tofogliflozin-a-selective-inhibitor-of-sodium-glucose-cotransporter-2-improves-arterial-stiffness-evaluated-by-cardio-ankle-vascular-index-in-patients-with-type-2-diabetes
#4
Nobuhiro Tahara, Sho-Ichi Yamagish, Munehisa Bekki, Atsuko Tahara, Sachiyo Igata, Akihiro Honda, Yoichi Sugiyama, Tomohisa Nakamura, Jiahui Sun, Yuki Kumashiro, Takanori Matsui, Yoshihiro Fukumoto
BACKGROUND: We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in type 2 diabetes mellitus (T2DM) patients compared with an equivalent hypoglycemic agent, glimepiride. However, it remains unclear whether and how switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. METHODS: Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study...
May 15, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29764742/synthesis-and-biological-evaluation-of-6-hydroxyl-c-aryl-glucoside-derivatives-as-novel-sodium-glucose-co-transporter-2-sglt2-inhibitors
#5
Xiaoyu Zhao, Bin Sun, Hongbo Zheng, Jun Liu, Lilin Qian, Xiaoning Wang, Hongxiang Lou
The sodium glucose co-transporter 2 (SGLT2) was considered as an important target for the treatment of type 2 diabetes mellitus in recent years. This report describes the design and synthesis of a series of novel SGLT2 inhibitors (11a-17a) as well as their dehydrate dihydrofuran derivatives (11b-17b), which were prepared by Mitsunobu reaction. Their SGLT2 inhibitory activity was also evaluated, and 16a and 17a were found to be the most potent compounds with IC50 values of 0.63 and 0.81 nM, respectively. However, all the dehydrate derivatives lose the SGLT2 inhibitory activity, with inhibition percentage no more than 66...
May 3, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29751356/exploring-novel-pharmacotherapeutic-applications-and-repurposing-potential-of-sodium-glucose-cotransporter-2-sglt2-inhibitors
#6
REVIEW
Tushar Madaan, Ibraheem Husain, Mohamad Akhtar, Abul Kalam Najmi
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of anti-hyperglycemic drugs with a distinctive mechanism of action focusing on renal absorption ofglucose. Apart from its anti-hyperglycemic effects, a multitude of research studies on this classhave revealed that these drugs have far more versatile and comprehensive pharmacologicaleffects than previously believed. Approximately 30% of FDA approved drugs are repurposedand used for indications other than those they were initially intended for...
May 11, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29751237/current-anti-diabetic-agents-and-their-molecular-targets-a-review
#7
REVIEW
Nagaraju Kerru, Ashona Singh-Pillay, Paul Awolade, Parvesh Singh
Diabetes mellitus is a medical condition characterized by the body's loss of control over blood sugar. The frequency of diagnosed cases and consequential increases in medical costs makes it a rapidly growing chronic disease that threatens human health worldwide. In addition, its unnerving statistical projections are perilous to both the economy of the nation and man's life expectancy. Type-I and type-II diabetes are the two clinical forms of diabetes mellitus. Type-II diabetes mellitus (T2DM) is illustrated by the abnormality of glucose homeostasis in the body, resulting in hyperglycemia...
May 3, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29750107/changes-in-heart-rate-in-patients-with-type-2-diabetes-mellitus-after-treatment-with-luseogliflozin-subanalysis-of-placebo-controlled-double-blind-clinical-trials
#8
Motoaki Sano, Shi Chen, Hisae Imazeki, Hidekazu Ochiai, Yutaka Seino
We evaluated the changes in heart rate on the treatment with SGLT2 inhibitor, luseogliflozin, in Japanese patients with type 2 diabetes mellitus (T2DM). It is suggested that luseogliflozin can effectively decrease in heart rate in patients with higher baseline.
May 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29749749/recent-progress-of-sodium-glucose-transporter-2-inhibitors-as-potential-antidiabetic-agents
#9
Yajing Zhang, Huazhuo Ban, Runan Yu, Zhijian Wang, Dayong Zhang
SGLT2 inhibitors were promising and novel antidiabetic drugs which suppressed glucose reabsorption and increased urinary glucose exertion. This review paper are aimed to summarize the recent progress of SGLT2 inhibitors during the last 5 years. This paper first summarizes the information of SGLT2 inhibitors, including mechanism, evolution and then focuses on the recent efforts on structure-activity relationships and structural optimization of SGLT2 inhibitors. Finally, the corresponding clinical therapeutic efficacy and adverse drug reaction in patients with Type 2 diabetes are discussed in detail...
May 11, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29747423/use-of-diabetes-treatment-satisfaction-questionnaire-in-diabetes-care-importance-of-patient-reported-outcomes
#10
REVIEW
Yoshifumi Saisho
The efficacy of diabetes treatment should not be evaluated solely by HbA1c levels as they should also focus on patient-reported outcomes (PROs), such as patient satisfaction, wellbeing and quality of life. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) has been developed to assess patient satisfaction with diabetes treatment. DTSQ has been translated into more than 100 languages and is widely used in many countries, since it is relatively easy to answer and is used for both patients with and without medical therapy...
May 9, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29737015/therapeutic-agents-targeting-cardiometabolic-risk-for-preventing-and-treating-atherosclerotic-cardiovascular-diseases
#11
Benoit J Arsenault, Nicolas Perrot, Rishi Puri
Targeting atherogenic lipoprotein levels with statins remains the current cornerstone of atherosclerotic cardiovascular disease (ACVD) management. In patients at high ACVD risk who cannot achieve the desired low-density lipoprotein (LDL) cholesterol target, the addition of compounds such as ezetimibe and proprotein subtilisin/kexin type-9 (PCSK9) inhibitors incrementally lowers cardiovascular risk. New glucose-lowering drugs such as glucacon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors were also shown to improve cardiometabolic risk factors and provide cardiovascular benefits in patients with type 2 diabetes...
May 8, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29735306/renoprotective-effects-of-sodium-glucose-cotransporter-2-inhibitors
#12
REVIEW
Hiddo J L Heerspink, Mikhail Kosiborod, Silvio E Inzucchi, David Z I Cherney
Over the past two years, our understanding of anti-hyperglycemic medications used to treat patients with type 2 diabetes (T2D) has fundamentally changed. Before the EMPA-REG OUTCOME trial, agents used to lower blood glucose were felt to prevent or delay the development of microvascular complications, but were not known to definitively reduce cardiovascular risk or mortality. Previous studies with then novel sodium-glucose cotransport-2 (SGLT2) inhibitors demonstrated improvements in several cardiovascular and renal risk factors, including HbA1c, blood pressure, weight, renal hyperfiltration, and albuminuria...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29732161/rapid-onset-diabetic-ketoacidosis-secondary-to-nivolumab-therapy
#13
Senhong Lee, Aparna Morgan, Sonali Shah, Peter R Ebeling
We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non-small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29717156/high-basolateral-glucose-increases-sodium-glucose-cotransporter-2-and-reduces-sirtuin-1-in-renal-tubules-through-glucose-transporter-2-detection
#14
Hiroyuki Umino, Kazuhiro Hasegawa, Hitoshi Minakuchi, Hirokazu Muraoka, Takahisa Kawaguchi, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+ -dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29709913/protective-effect-of-ipragliflozin-on-pancreatic-islet-cells-in-obese-type-2-diabetic-db-db-mice
#15
Toshiyuki Takasu, Shoji Takakura
Ipragliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that increases urinary glucose excretion and subsequently improves hyperglycemia in patients with type 2 diabetes mellitus (T2DM). To assess the beneficial effect of ipragliflozin on the mass and function of pancreatic β-cells under diabetic conditions, obese T2DM db/db mice were treated with ipragliflozin for 5 weeks. Glucose and lipid metabolism parameters, pathological changes in pancreatic islet cells and insulin content were evaluated...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29708925/unexplained-reciprocal-regulation-of-diabetes-and-lipoproteins
#16
Sei Higuchi, M Concepción Izquierdo, Rebecca A Haeusler
PURPOSE OF REVIEW: Type 2 diabetes is associated with a characteristic dyslipidemia that may exacerbate cardiovascular risk. The causes of, and the effects of new antihyperglycemia medications on, this dyslipidemia, are under investigation. In an unexpected reciprocal manner, lowering LDL-cholesterol with statins slightly increases the risk of diabetes. Here we review the latest findings. RECENT FINDINGS: The inverse relationship between LDL-cholesterol and diabetes has now been confirmed by multiple lines of evidence...
June 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29707088/impact-of-dapagliflozin-therapy-on-renal-protection-and-kidney-morphology-in-patients-with-uncontrolled-type-2-diabetes-mellitus
#17
Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Akira Yoshida, Katsunori Jinnouchi, Motoko Tanaka, Hiroyuki Nishimura, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi
Background: We examined whether the sodium-glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin can improve urine albumin-to-creatinine ratio (UACR) associated with a reduction in body weight or body fat in patients with type 2 diabetes mellitus (T2DM). Methods: We prospectively recruited T2DM patients having inadequate glycemic control (hemoglobin A1c (HbA1c) > 7.0%) not on SGLT2i therapy. We treated the patients with add-on dapagliflozin treatment or intensification of non-SGLT2 inhibitor therapies for 6 months...
June 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29704192/sglt2-inhibition-and-heart-failure-current-concepts
#18
REVIEW
Joaquim Silva Custodio, Andre Rodrigues Duraes, Marconi Abreu, Natalia Albuquerque Rocha, Leonardo Roever
Type 2 diabetes mellitus (T2DM) is a major risk factor for several cardiovascular (CV) conditions, including heart failure (HF). However, until recently, no therapy to treat patients with diabetes could also reduce CV risks related to HF. The EMPA-REG OUTCOME trial with empagliflozin was the first to demonstrate significant cardioprotective benefits in this population. Its impressive 35% reduction in hospitalizations for HF drew the attention of the scientific community to the possibility that pharmacologic sodium-glucose cotransporter 2 (SGLT2) inhibition could be part of the armamentarium for treating patients with HF, with and without diabetes...
April 28, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29703207/sglt2-inhibition-via-dapagliflozin-improves-generalized-vascular-dysfunction-and-alters-the-gut-microbiota-in-type-2-diabetic-mice
#19
Dustin M Lee, Micah L Battson, Dillon K Jarrell, Shuofei Hou, Kayl E Ecton, Tiffany L Weir, Christopher L Gentile
BACKGROUND: Type 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism...
April 27, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29702076/prevention-of-progression-of-diabetic-nephropathy-by-the-sglt2-inhibitor-ipragliflozin-in-uninephrectomized-type-2-diabetic-mice
#20
Atsuo Tahara, Toshiyuki Takasu
Diabetic nephropathy is the leading cause of end-stage renal disease in the world. Although recent development of sodium-glucose cotransporter (SGLT) 2 inhibitors offers a new antidiabetic therapeutic strategy, it remains unclear whether such treatments are beneficial for limiting the progression of type 2 diabetic overt nephropathy. This study examined the effect of the SGLT2 inhibitor ipragliflozin on the progression of nephropathy in uninephrectomized KK/Ay type 2 diabetic mice, which exhibit not only typical diabetic symptoms such as hyperglycemia, hyperinsuemia, glucose intolerance, insulin resistance, hyperlipidemia, inflammation, and obesity, but also moderate hypertension and overt nephropathy with decline in renal function...
April 24, 2018: European Journal of Pharmacology
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