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https://www.readbyqxmd.com/read/28928461/time-dependent-effects-of-ipragliflozin-on-behaviour-and-energy-homeostasis-in-normal-and-type-2-diabetic-rats-continuous-glucose-telemetry-analysis
#1
Hiroyuki Iuchi, Masaya Sakamoto, Daisuke Matsutani, Hirofumi Suzuki, Yosuke Kayama, Norihiko Takeda, Susumu Minamisawa, Kazunori Utsunomiya
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote urinary glucose excretion. Conversely, they cause behavioural changes, such as hyperphagia, that result in a positive energy balance. The relationship between energy homeostasis and SGLT2 inhibitors-induced behavioural changes remains unclear. Here we show that ipragliflozin, a SGLT2 inhibitor, time-dependently affects behaviour and enhances energy expenditure in normal and type 2 diabetic Goto-Kakizaki (GK) rats, using continuous glucose telemetry...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928093/effect-of-sodium-glucose-cotransporter-2-sglt2-inhibition-on-weight-loss-is-partly-mediated-by-liver-brain-adipose-neurocircuitry
#2
Yoshikazu Sawada, Yoshihiko Izumida, Yoshinori Takeuchi, Yuichi Aita, Nobuhiro Wada, EnXu Li, Yuki Murayama, Xiaoying Piao, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Takashi Kadowaki, Hitoshi Shimano, Naoya Yahagi
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28926495/bolstering-your-armamentarium-with-sglt2-inhibitors
#3
Lucia M Novak, Davida F Kruger
Sodium-glucose cotransporter-2 inhibitors have a unique mechanism of action in the kidneys that causes glucosuria, which lowers plasma glucose. They are also associated with reduced body weight and BP, and a low incidence of hypoglycemia. This article reviews the pharmacologic profiles and clinical implications of canagliflozin, dapagliflozin, and empagliflozin.
October 18, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28924948/magnetic-nanoparticles-for-the-delivery-of-dapagliflozin-to-hypoxic-tumors-physicochemical-characterization-and-cell-studies
#4
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/28924123/the-improvement-of-the-hepatic-histological-findings-in-a-patient-with-non-alcoholic-steatohepatitis-with-type-2-diabetes-after-the-administration-of-the-sodium-glucose-cotransporter-2-inhibitor-ipragliflozin
#5
Akihiko Takeda, Aya Irahara, Atsuko Nakano, Emi Takata, Yuko Koketsu, Kunie Kimata, Eri Senda, Hajime Yamada, Kazuhito Ichikawa, Takahiro Fujimori, Yoshio Sumida
The patient was a 67-year-old woman with type 2 diabetes and non-alcoholic steatohepatitis (NASH). The administration of the sodium-glucose cotransporter 2 (SGLT2) inhibitor, ipragliflozin improved her liver dysfunction clinically and histologically. The serum alanine aminotransferase (ALT) and ferritin levels decreased to normal limits after treatment for four months. Type IV collagen and hyaluronic acid, both of which were serum fibrotic markers, decreased after treatment. Ultrasonography and computed tomography showed a decrease in the fat deposits in her liver...
September 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28919060/sglt2-inhibitors-in-type-1-diabetes-knocked-down-but-up-again
#6
John R Petrie
No abstract text is available yet for this article.
September 13, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28916336/renal-tubular-and-adrenal-medullary-tumors-in-the-2-year-rat-study-with-canagliflozin-confirmed-to-be-secondary-to-carbohydrate-glucose-malabsorption-in-the-15-month-mechanistic-rat-study
#7
Sandra De Jonghe, Mark D Johnson, Rao N V S Mamidi, Petra Vinken, Bianca Feyen, Godelieve Lammens, Jim Proctor
During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet...
September 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28912902/effects-of-dapagliflozin-on-body-composition-and-liver-tests-in-patients-with-nonalcoholic-steatohepatitis-associated-with-type-2-diabetes-mellitus-a-prospective-open-label-uncontrolled-study
#8
Hiroshi Tobita, Shuichi Sato, Tatsuya Miyake, Shunji Ishihara, Yoshikazu Kinoshita
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an active form of nonalcoholic fatty liver disease. Risk factors for NASH include type 2 diabetes mellitus (T2DM) and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors used to treat T2DM prevent glucose reabsorption in the kidney and increase glucose urinary excretion. Dapagliflozin is a potent, selective SGLT2 inhibitor that reduces hyperglycemia in patients with T2DM and has been demonstrated to reduce some complications associated with NASH in rodent models...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28911306/management-of-blood-pressure-and-heart-rate-in-patients-with-diabetes-mellitus
#9
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/28900540/treatment-of-diabetic-mice-with-the-sglt2-inhibitor-ta-1887-antagonizes-diabetic-cachexia-and-decreases-mortality
#10
Taichi Sugizaki, Shunshun Zhu, Ge Guo, Akiko Matsumoto, Jiabin Zhao, Motoyoshi Endo, Haruki Horiguchi, Jun Morinaga, Zhe Tian, Tsuyoshi Kadomatsu, Keishi Miyata, Hiroshi Itoh, Yuichi Oike
A favorable effect of an inhibitor of the sodium-glucose cotransporter 2 (SGLT2i) on mortality of diabetic patients was recently reported, although mechanisms underlying that effect remained unclear. Here, we examine SGLT2i effects on survival of diabetic mice and assess factors underlying these outcomes. To examine SGLT2i treatment effects in a model of severe diabetes, we fed genetically diabetic db/db mice a high-fat diet and then assessed outcomes including diabetic complications between SGLT2i TA-1887-treated and control mice...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28898514/risk-of-lower-extremity-amputations-in-patients-with-type-2-diabetes-mellitus-treated-with-sglt2-inhibitors-in-the-united-states-a-retrospective-cohort-study
#11
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 inhibitors (SGLT2i) overall, and canagliflozin specifically, compared with non-SGLT2i antihyperglycemic agents (AHAs). MATERIALS AND METHODS: Patients with T2DM newly exposed to SGLT2i or non-SGLT2i AHAs were identified using the Truven MarketScan database. The incidence of below-knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2i, canagliflozin, or non-SGLT2i AHAs...
September 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28879786/pharmacological-management-of-type-2-diabetes-what-s-new-in-2017
#12
André J Scheen
Introduction Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas covered Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients...
September 7, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28872686/weak-bones-in-diabetes-mellitus-an-update-on-pharmaceutical-treatment-options
#13
REVIEW
Daphne P L Lin, Crispin R Dass
OBJECTIVES: Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones...
September 5, 2017: Journal of Pharmacy and Pharmacology
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
#14
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
#15
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/28861952/use-of-sodium-glucose-cotransporter%C3%A2-2-inhibitors-in-older-patients-with-type%C3%A2-2-diabetes-mellitus
#16
Takahiro Kambara, Rei Shibata, Hiroyuki Osanai, Yoshihito Nakashima, Hiroshi Asano, Kazuyoshi Sakai, Toyoaki Murohara, Masayoshi Ajioka
AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. METHODS: A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. RESULTS: The mean age of the patients was 73...
September 1, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28860019/pooled-analysis-of-phase-iii-trials-indicate-contrasting-influences-of-renal-function-on-blood%C3%A2-pressure-body-weight-and-hba1c-reductions-with-empagliflozin
#17
David Z I Cherney, Mark E Cooper, Ilkka Tikkanen, Egon Pfarr, Odd Erik Johansen, Hans J Woerle, Uli C Broedl, Søren S Lund
Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce HbA1c, blood pressure, and weight in patients with type 2 diabetes. To investigate the effect of renal function on reductions in these parameters with the SGLT2 inhibitor empagliflozin, we assessed subgroups by baseline estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) in pooled data from five 24-week trials of 2286 patients with type 2 diabetes randomized to empagliflozin or placebo. Reductions in HbA1c with empagliflozin versus placebo significantly diminished with decreasing baseline eGFR...
August 28, 2017: Kidney International
https://www.readbyqxmd.com/read/28857451/effect-of-ertugliflozin-on-glucose-control-body-weight-blood-pressure-and-bone-density-in-type-2-diabetes-mellitus-inadequately-controlled-on-metformin-monotherapy-vertis-met
#18
Julio Rosenstock, Juan Frias, Dénes Páll, Bernard Charbonnel, Raluca Pascu, Didier Saur, Amanda Darekar, Susan Huyck, Harry Shi, Brett Lauring, Steven G Terra
INTRODUCTION: We evaluated efficacy and safety of ertugliflozin, an SGLT2 inhibitor, in type 2 diabetes mellitus (T2DM) inadequately controlled (HbA1c, 7.0-10.5%) on metformin monotherapy (≥1500 mg/day for ≥8 weeks). METHODS: Double-blind, 26-week, multicentre study with ongoing 78-week extension; 621 participants randomized 1:1:1 to placebo, ertugliflozin 5 or 15 mg/day. Primary endpoint: change from baseline in HbA1c at week 26. Secondary efficacy endpoints: change from baseline at week 26 in fasting plasma glucose (FPG), body weight, systolic/diastolic blood pressure (SBP/DBP); participants with HbA1c <7...
August 31, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28856166/ketoacidosis-with-canagliflozin-prescribed-for-phosphoinositide-3-kinase-inhibitor-induced-hyperglycemia-a-case-report
#19
Christopher Bowman, Vandana Abramson, Melissa Wellons
Context. Many phosphoinositide-3-kinase (PI3K) inhibitors are under trial for cancer treatment. We present a patient taking taselisib who developed ketoacidosis within 1 week of starting canagliflozin. Case Description. A 69-year-old female patient with no previous history of diabetes mellitus was enrolled in a clinical trial for taselisib therapy in stage IV breast cancer. Hyperglycemia treatment with metformin was insufficient and not tolerated. The addition of canagliflozin daily resulted in ketoacidosis and hospitalization within 1 week...
July 2017: Journal of Investigative Medicine High Impact Case Reports
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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