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SGLT2 inhibitors

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https://www.readbyqxmd.com/read/28635308/combined-hqsar-topomer-comfa-homology-modeling-and-docking-studies-on-triazole-derivatives-as-sglt2-inhibitors
#1
Shuling Yu, Jintao Yuan, Yi Zhang, Shufang Gao, Ying Gan, Meng Han, Yuewen Chen, Qiaoqiao Zhou, Jiahua Shi
AIM: Sodium-glucose cotransporter 2 (SGLT2) is a promising target for diabetes therapy. We aimed to develop computational approaches to identify structural features for more potential SGLT2 inhibitors. MATERIALS & METHODS: In this work, 46 triazole derivatives as SGLT2 inhibitors were studied using a combination of several approaches, including hologram quantitative structure-activity relationships (HQSAR), topomer comparative molecular field analysis (CoMFA), homology modeling, and molecular docking...
June 21, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28634592/euglycemic-diabetic-ketoacidosis-with-prolonged-glucosuria-associated-with-the-sodium-glucose-cotransporter-2-canagliflozin
#2
Daniel A Kelmenson, Kelsey Burr, Yusra Azhar, Paul Reynolds, Chelsea A Baker, Neda Rasouli
Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control by a reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. This unique mechanism, independent of insulin secretion and beta cell function, has made this class of medication desirable in patients with type 2 diabetes. However in May 2015, the US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors...
April 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28630133/dual-regulation-of-gluconeogenesis-by-insulin-and-glucose-in-the-proximal-tubules-of-the-kidney
#3
Motohiro Sasaki, Takayoshi Sasako, Naoto Kubota, Yoshitaka Sakurai, Iseki Takamoto, Tetsuya Kubota, Reiko Inagi, George Seki, Moritaka Goto, Kohjiro Ueki, Masaomi Nangaku, Takahito Jomori, Takashi Kadowaki
Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. Here, we found that PT-specific IRS1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter-2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. On the other hand, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor...
June 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28621337/diabetes-sglt2-inhibitors-and-diabetic-ketoacidosis-a-growing-concern
#4
Guillermo E Umpierrez
No abstract text is available yet for this article.
June 16, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28619659/effects-of-canagliflozin-on-cardiovascular-biomarkers-in-older-adults-with-type-2-diabetes
#5
James L Januzzi, Javed Butler, Petr Jarolim, Naveed Sattar, Ujjwala Vijapurkar, Mehul Desai, Michael J Davies
BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: To examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM. METHODS: In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, we assessed median percent change in serum N-terminal pro-B type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI) , soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks...
June 9, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28616806/ipragliflozin-reduces-epicardial-fat-accumulation-in-non-obese-type-2-diabetic-patients-with-visceral-obesity-a-pilot-study
#6
Tatsuya Fukuda, Ryotaro Bouchi, Masahiro Terashima, Yuriko Sasahara, Masahiro Asakawa, Takato Takeuchi, Yujiro Nakano, Masanori Murakami, Isao Minami, Hajime Izumiyama, Koshi Hashimoto, Takanobu Yoshimoto, Yoshihiro Ogawa
INTRODUCTION: Epicardial fat (EF) was reported to be independently associated with cardiovascular disease regardless of obesity. We have previously reported that a sodium-glucose co-transporter-2 (SGLT2) inhibitor, luseogliflozin, reduces the EF volume (EFV) in parallel with the reduction of body weight in obese patients (BMI ≥25 kg/m(2)) with type 2 diabetes. However, it is unknown whether SGLT2 inhibitors could reduce EFV in non-obese patients (BMI <25 kg/m(2)) with type 2 diabetes...
June 14, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28611861/effects-of-six-kinds-of-sodium-glucose-cotransporter-2-inhibitors-on-metabolic-parameters-and-summarized-effect-and-its-correlations-with-baseline-data
#7
Hidekatsu Yanai, Mariko Hakoshima, Hiroki Adachi, Akiko Kawaguchi, Yoko Waragai, Tadanao Harigae, Yoshinori Masui, Kouki Kakuta, Hidetaka Hamasaki, Hisayuki Katsuyama, Tomoko Kaga, Akahito Sako
BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) blocks reabsorption of glucose by inhibiting SGLT2 in kidney, promotes the renal excretion of glucose and improves blood glucose control without requiring insulin secretion. Anti-atherosclerotic effects of SGLT2is have not been fully elucidated until today. METHODS: We retrospectively picked up patients with type 2 diabetes who had been continuously prescribed SGLT2i for 3 months or more between April 2014 and December 2016 by a chart-based analysis, and compared metabolic parameters including coronary risk factors before the SGLT2i treatment with the data at 3 and 6 months after the SGLT2i treatment started...
July 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28606346/empa-reg-outcome-the-nephrologist-s-point-of-view
#8
Christoph Wanner
There is increasing evidence that sodium glucose cotransporter 2 (SGLT2) inhibitors have renoprotective effects, as demonstrated by the renal analyses from clinical trials including Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), CANagliflozin Treatment And Trial Analysis versus SUlphonylurea (CANTATA-SU), and the dapagliflozin renal study. The potential mechanisms responsible are likely multifactorial, and direct renovascular and hemodynamic effects are postulated to play a central role...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28606344/empa-reg-outcome-the-endocrinologist-s-point-of-view
#9
Leigh Perreault
For many years, it was widely accepted that control of plasma lipids and blood pressure could lower macrovascular risk in patients with type 2 diabetes mellitus (T2DM), whereas the benefits of lowering plasma glucose were largely limited to improvements in microvascular complications. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) study demonstrated for the first time that a glucose-lowering agent, the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, could reduce major adverse cardiovascular events, cardiovascular mortality, hospitalization for heart failure, and overall mortality when given in addition to standard care in patients with T2DM at high cardiovascular risk...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28601988/surgical-and-advanced-medical-therapy-for-the-treatment-of-type-2-diabetes-in-class-i-obese-patients-a-short-term-outcome
#10
Mohit Bhandari, Winni Mathur, Ravindra Kumar, Arun Mishra, Mahak Bhandari
BACKGROUND: Bariatric surgery, incretin-based therapy (glucagon-like peptide-1 analogues), and sodium-glucose co-transporter 2 (SGLT2) inhibitors have antidiabetic properties in morbidly obese patients. However, their comparative efficacy in treating type 2 diabetes mellitus (T2DM) in class I obese patients specifically in Indian has not been studied yet. This study evaluates and compares the efficacy and side effect of surgical and advanced medical management of T2DM in class I obese patients...
June 11, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28598954/role-of-the-sympathetic-nervous-system-in-regulation-of-the-sodium-glucose-cotransporter-2
#11
Vance B Matthews, Rosemary H Elliot, Caroline Rudnicka, Jana Hricova, Lakshini Herat, Markus P Schlaich
BACKGROUND: The sympathetic nervous system (SNS) regulates glucose metabolism in various organs including the kidneys. The sodium glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in renal proximal tubules and its inhibition has been shown to improve glucose control, cardiovascular and renal outcomes. We hypothesized that SNS-induced alterations of glucose metabolism may be mediated via regulation of SGLT2. METHOD: We used human renal proximal tubule cells to investigate the effects of noradrenaline on SGLT2 regulation...
June 8, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28597228/sglt2-i-in-the-hospital-setting-diabetic-ketoacidosis-and-other-benefits-and-concerns
#12
REVIEW
Joshua A Levine, Susan L Karam, Grazia Aleppo
PURPOSE OF REVIEW: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents. They are increasingly being prescribed in the outpatient diabetic population. In this review, we examine the risks and benefits of continuation and initiation of SGLT2 inhibitors in the inpatient setting. RECENT FINDINGS: There are currently no published data regarding safety and efficacy of SGLT2 inhibitor use in the hospital. Outpatient data suggests that SGLT2 inhibitors have low hypoglycemic risk...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28596840/novel-sglt2-inhibitor-first-in-man-studies-of-antisense-compound-is-associated-with-unexpected-renal-effects
#13
Leonie van Meer, Marloes van Dongen, Matthijs Moerland, Marieke de Kam, Adam Cohen, Jacobus Burggraaf
The antisense compound ISIS 388626 selectively inhibits renal glucose reabsorption by inhibiting the sodium-glucose cotransporter-2 (SGLT2) mRNA expression. It is developed as an insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The safety, tolerability, pharmacokinetics, and pharmacodynamics after subcutaneous administration of the drug were planned to be evaluated in healthy volunteers in a single-ascending-dose study (50-400 mg) and a multiple-ascending-dose study (6 weeks; weekly doses of 50-400 mg with loading dose regimen of three doses during the first week)...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28596160/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-urinary-excretion-of-intact-and-total-angiotensinogen-in-patients-with-type-2-diabetes
#14
Takuo Yoshimoto, Takayuki Furuki, Hiroyuki Kobori, Masaaki Miyakawa, Hitomi Imachi, Koji Murao, Akira Nishiyama
We conducted a descriptive case study to examine the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on urinary angiotensinogen excretion, which represents the function of the intrarenal renin-angiotensin system, in patients with type 2 diabetes. An SGLT2 inhibitor (canagliflozin 100 mg/day, ipragliflozin 25 mg/day, dapagliflozin 5 mg/day, luseogliflozin 2.5 mg/day or tofogliflozin 20 mg/day) was administered for 1 month (n=9). ELISA kits were used to measure both urinary intact and total angiotensinogen levels...
June 8, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28594482/non-severe-hypoglycemia-risk-difference-between-sulfonylurea-and-sodium-glucose-cotransporter-2-inhibitors-sglt2-i-as-an-add-on-to-metformin-in-randomized-controlled-trials
#15
Pendar Farahani
BACKGROUND: Non-severe hypoglycemia reduces well-being, lowers quality of life, reduces productivity and increases treatment costs. The non-severe hypoglycemia rate, attributable to sulfonylurea (SU) utilization compared with newer classes such as SGLT2-I, could be of clinical significance. OBJECTIVES: To explore the non-severe hypoglycemia risk difference (RD) for SU use compared with SGLT2-I in randomized controlled trials (RCTs) as an add on to metformin. METHODS: A search was conducted for RCTs of SGLT2-I...
May 23, 2017: Journal of Population Therapeutics and Clinical Pharmacology
https://www.readbyqxmd.com/read/28593615/a-single-dose-of-dapagliflozin-an-sglt-2-inhibitor-induces-higher-glycosuria-in-gck-and-hnf1a-mody-than-in-type-2-diabetes-mellitus
#16
J Hohendorff, M Szopa, J Skupien, M Kapusta, B Zapala, T Platek, S Mrozinska, T Parpan, W Glodzik, A Ludwig-Galezowska, B Kiec-Wilk, T Klupa, M T Malecki
AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes...
June 7, 2017: Endocrine
https://www.readbyqxmd.com/read/28591538/risk-of-diabetic-ketoacidosis-after-initiation-of-an-sglt2-inhibitor
#17
LETTER
Michael Fralick, Sebastian Schneeweiss, Elisabetta Patorno
New England Journal of Medicine, Volume 376, Issue 23, Page 2300-2302, June 2017.
June 8, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28589154/prolonged-ketosis-in-a-patient-with-euglycemic-diabetic-ketoacidosis-secondary-to-dapagliflozin
#18
Shreya Pujara, Adriana Ioachimescu
Since the approval of sodium-glucose cotransporter 2 (SGLT2) inhibitors by the US Food and Drug Administration for type 2 diabetes, there have been several reports of euglycemic diabetic ketoacidosis in patients using this class of medication. We present a case of euglycemic diabetic ketoacidosis where ketonemia and glucosuria persisted well beyond the expected effect of dapagliflozin. Our patient is a 50-year-old woman with type 2 diabetes since age 35 who was taking metformin and dapagliflozin. She presented with fatigue, constipation, and 3 days of reduced oral intake...
April 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28588816/diabetic-ketoacidosis-inducing-myocardial-infarction-secondary-to-treatment-with-dapagliflozin-a-case-report
#19
José M Gil-Perdomo, Tomás F Fariña González, Benjamín Jordán-Arias, Sara Domingo-Marín, Juan J González Armengol, Fernando Martínez-Sagasti
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are able to provoke diabetic ketoacidosis (DKA) with absence or low levels of ketone bodies in urine and slightly elevated blood glucose levels, which could delay the diagnosis; however, the presence of high urine output, due to the excretion of glucose, can help to identify the true cause.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28588220/effects-of-sglt2-inhibitors-on-utis-and-genital-infections-in-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis
#20
Jiali Liu, Ling Li, Sheyu Li, Pengli Jia, Ke Deng, Wenwen Chen, Xin Sun
Previous trial evidence suggested potential risk of serious urinary tract infections (UTIs) and genital infections in type 2 diabetes patients using sodium glucose co-transporter-2 inhibitors (SGLT2) inhibitors. We conducted a systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on UTIs and genital infections in patients with type 2 diabetes. In total, 77 RCTs involving 50,820 participants were eligible. The meta-analyses of randomized controlled trials (RCTs) showed no significant difference in UTIs between SGLT2 inhibitors versus control (2,526/29,086 vs...
June 6, 2017: Scientific Reports
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