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Canagliflozin

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https://www.readbyqxmd.com/read/28090050/euglycemic-diabetic-ketoacidosis-with-persistent-diuresis-treated-with-canagliflozin
#1
Junichiro Adachi, Yuusuke Inaba, Chisato Maki
Diabetic ketoacidosis is characterized by hyperglycemia, anion-gap acidosis, and increased plasma ketones. After the resolution of hyperglycemia, persistent diuresis is rare. We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia. Physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with SGLT2 inhibitors...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28039605/pharmacokinetic-characteristics-and-clinical-efficacy-of-an-sglt2-inhibitor-plus-dpp-4-inhibitor-combination-therapy-in-type-2-diabetes
#2
REVIEW
André J Scheen
Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin)...
December 30, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27995594/liraglutide-versus-sglt-2-inhibitors-in-people-with-type-2-diabetes-a-network-meta-analysis
#3
Maria Lorenzi, Uffe Jon Ploug, Jakob Langer, Rasmus Skovgaard, Michael Zoratti, Jeroen Jansen
INTRODUCTION: For people with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs (OADs), evidence from both randomized controlled trials (RCTs) and real-world studies has demonstrated that treatment intensification with liraglutide offers effective glycemic control, weight reduction, and a lower risk of hypoglycemia compared to treatment intensification with insulin or additional OADs. Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a new class of OADs that have also been shown to be effective in T2DM patients inadequately controlled with OADs...
December 19, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27989651/the-impact-of-sglt2-inhibitors-compared-with-insulin-on-diabetic-bone-disease-in-a-mouse-model-of-type-1-diabetes
#4
Kathryn M Thrailkill, Jeffry S Nyman, R Clay Bunn, Sasidhar Uppuganti, Katherine L Thompson, Charles K Lumpkin, Evangelia Kalaitzoglou, John L Fowlkes
Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover...
October 28, 2016: Bone
https://www.readbyqxmd.com/read/27981497/factors-affecting-canagliflozin-induced-transient-urine-volume-increase-in-patients-with-type-2-diabetes-mellitus
#5
Hiroyuki Tanaka, Kazuhiko Takano, Hiroaki Iijima, Hajime Kubo, Nobuko Maruyama, Toshio Hashimoto, Kenji Arakawa, Masanori Togo, Nobuya Inagaki, Kohei Kaku
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. METHODS: Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days...
December 15, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27977934/longer-term-safety-and-tolerability-of-canagliflozin-in-patients-with-type-2-diabetes-a-pooled-analysis
#6
Rong Qiu, Dainius Balis, John Xie, Michael J Davies, Mehul Desai, Gary Meininger
OBJECTIVE: To evaluate the longer-term safety of canagliflozin, an SGLT2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: The safety/tolerability of canagliflozin 100 and 300mg were assessed using data pooled from 7 placebo- and active-controlled studies of 52-104 weeks in duration that enrolled a broad range of patients with T2DM (N = 5598). Canagliflozin 100 and 300mg as monotherapy or in combination with various background antihyperglycemic agents (AHAs) were compared with pooled non-canagliflozin treatments (ie, placebo, sitagliptin, glimepiride)...
December 15, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27977314/diabetes-and-kidney-disease-the-role-of-sodium-glucose-cotransporter-2-sglt-2-and-sglt-2-inhibitors-in-modifying-disease-outcomes
#7
Christian W Mende
Patients with type 2 diabetes (T2D) often have coexisting chronic kidney disease (CKD). However, healthy renal function is crucial in maintaining glucose homeostasis, assuring that almost all of the filtered glucose is reabsorbed by the sodium glucose cotransporters (SGLTs) SGLT-1 and SGLT-2. In diabetes, an increased amount of glucose is filtered by the kidneys and SGLT-2 is upregulated, leading to increased glucose absorption and worsening hyperglycemia. Prolonged hyperglycemia contributes to the development of CKD by inducing metabolic and hemodynamic changes in the kidneys...
January 4, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27933185/circulating-serpinb1-levels-and-clinical-features-in-patients-with-type-2-diabetes
#8
Kohzo Takebayashi, Kenji Hara, Tomoko Terasawa, Rika Naruse, Mariko Suetsugu, Takafumi Tsuchiya, Toshihiko Inukai
OBJECTIVE: The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic β cells, and may decrease insulin resistance...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/27931088/sglt2-inhibitors-a-systematic-review-of-diabetic-ketoacidosis-and-related-risk-factors-in-the-primary-literature
#9
Kelly R Burke, Christine A Schumacher, Spencer E Harpe
STUDY OBJECTIVE: There is currently minimal information regarding risk factors for the development of sodium-glucose cotransporter-2 inhibitor (SGLT2i)-related diabetic ketoacidosis (DKA). We aim to identify individual patient characteristics associated with cases of SGLT2i-related DKA to better describe potential risk factors. DESIGN: Systematic review of primary literature. PATIENTS: 34 case reports of patients with Type 1 and Type 2 Diabetes Mellitus who developed DKA while receiving an SGLT2i...
December 8, 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27928503/metabolic-ketoacidosis-with-normal-blood-glucose-a-rare-complication-of-sodium-glucose-cotransporter-2-inhibitors
#10
Saad Ullah, Noman Khan, Hassan Zeb, Hassan Tahir
Ketoacidosis is a significant and often a life-threatening complication of diabetes mellitus seen mostly in type 1 diabetes mellitus as well as occasionally in type 2 diabetes mellitus. Diabetic ketoacidosis usually manifests with high blood glucose more than 250 mg/dL, but euglycemic diabetic ketoacidosis is defined as ketoacidosis associated with blood glucose level less than 250 mg/dL. Normal blood glucose in such patients results in significant delay in diagnosis and management of diabetic ketoacidosis, thus increasing mortality and morbidity...
2016: SAGE open medical case reports
https://www.readbyqxmd.com/read/27918226/canagliflozin-use-in-type-i-diabetes-mellitus
#11
Robert Guthrie
Peters et al documented the appearance of diabetic ketoacidosis without significant elevation of serum glucose in patients treated with Canagliflozin. They solicited patient reports from their practice and from other colleagues' practices and identified nine patients, mainly with Type I Diabetes. Erondu et al evaluated the Canagliflozin development data base to describe the rate and appearance of ketoacidosis in the study patients. They found that in the research patients with Type 2 Diabetes, the rate of ketoacidosis in Canagliflozin patients was uncommon and similar to the reported rate in Type 2 patients not receiving Canagliflozin...
December 5, 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27902600/efficacy-and-safety-of-canagliflozin-in-patients-with-type-2-diabetes-a-meta-analysis-of-randomized-controlled-trials
#12
Wei Xiong, Ming Yue Xiao, Mei Zhang, Fei Chang
BACKGROUND: Canagliflozin is a new SGLT2 inhibitor which has been approved as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes (T2D) mellitus in more than 30 countries. To evaluate the efficacy and safety of canagliflozin in patients with T2D, we carried out a meta-analysis of phase III clinical trials to offer an additional evidence of the efficacy and safety of canagliflozin for evidence-based clinical practice, strictly restricting the treatment durations to 26 weeks (core period) and 52 weeks (extension period)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27899497/the-effect-of-canagliflozin-a-sodium-glucose-cotransporter-2-inhibitor-on-glycemic-end-points-assessed-by-continuous-glucose-monitoring-and-patient-reported-outcomes-among-people-with-type-1-diabetes
#13
Helena W Rodbard, Anne L Peters, April Slee, Anjun Cao, Shana B Traina, Maria Alba
OBJECTIVE: To assess the effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic parameters and measures of glucose variability assessed by a 9-point self-monitoring blood glucose (SMBG) and continuous glucose monitoring (CGM) profiles, and patient-reported outcomes as an add-on to insulin among participants with type 1 diabetes. RESEARCH DESIGN AND METHODS: In this randomized, double-blind study, 351 participants received canagliflozin 100 or 300 mg or placebo for 18 weeks...
November 29, 2016: Diabetes Care
https://www.readbyqxmd.com/read/27894216/bone-effects-of-canagliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-patients-with-type-2-diabetes-mellitus
#14
Thomas C Blevins, Azeez Farooki
Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. It has been reported that SGLT2 inhibitors may have potential adverse effects on bone, including increased fracture risk and decreased bone mineral density (BMD). Across clinical studies, canagliflozin was not associated with meaningful changes in serum or urine calcium, vitamin D, or parathyroid hormone...
November 28, 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27889414/changes-in-glucose-induced-plasma-active-glucagon-like-peptide-1-levels-by-co-administration-of-sodium-glucose-cotransporter-inhibitors-with-dipeptidyl-peptidase-4-inhibitors-in-rodents
#15
Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Hikida, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masabumi Minami, Masaharu Shiotani
We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27876617/canagliflozin-a-sodium-glucose-cotransporter-2-inhibitor-attenuates-obesity-induced-inflammation-in-the-nodose-ganglion-hypothalamus-and-skeletal-muscle-of-mice
#16
Farhana Naznin, Hideyuki Sakoda, Tadashi Okada, Hironobu Tsubouchi, T M Zaved Waise, Kenji Arakawa, Masamitsu Nakazato
Chronic inflammation in systemic organs, such as adipose tissue, nodose ganglion, hypothalamus, and skeletal muscles, is closely associated with obesity and diabetes mellitus. Because sodium glucose cotransporter 2 (SGLT2) inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of canagliflozin, an SGLT2 inhibitor, on obesity-induced inflammation in neural tissues and skeletal muscles of mice. High-fat diet (HFD)-fed male C57BL/6J mice were treated with canagliflozin for 8 weeks...
January 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27867961/cardio-renal-protection-with-empagliflozin
#17
Richard J MacIsaac, George Jerums, Elif I Ekinci
Cardiovascular (CV) and kidney disease are common and significant complications in people with type 2 diabetes (T2DM). CV disease is the leading cause of death, morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney disease is a major risk factor for CV disease and is the main reason why patients need renal replacement therapy. In this perspective, we highlight the results of the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose lowering medications, reduces death from CV causes, hospitalisation for heart failure and progression to end stage kidney disease in patients with T2DM and established CV disease...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27866701/place-of-sodium-glucose-cotransporter-2-inhibitors-in-east-asian-subjects-with-type-2-diabetes-mellitus-insights-into-the-management-of-asian-phenotype
#18
REVIEW
Lee Ling Lim, Alexander Tong Boon Tan, Kevin Moses, Viraj Rajadhyaksha, Siew Pheng Chan
The burden of type 2 diabetes (T2DM) in East Asia is alarming. Rapid modernization and urbanization have led to major lifestyle changes and a tremendous increase in the prevalence of obesity, metabolic syndrome, and diabetes mellitus. The development of T2DM at a younger age, with lower body mass index, higher visceral adiposity, and more significant pancreatic beta-cell dysfunction compared to Caucasians are factors responsible for the increased prevalence of T2DM in East Asians. Sodium-glucose Cotransporter-2 (SGLT2) inhibitors (canagliflozin, dapaglifozin, empagliflozin, etc...
October 15, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27862830/urinary-tract-and-genital-infections-in-patients-with-type-2-diabetes-treated-with-sodium-glucose-co-transporter-2-inhibitors-a-meta-analysis-of-randomized-controlled-trials
#19
Dandan Li, Tiansheng Wang, Su Shen, Zhenwei Fang, Yue Dong, Huilin Tang
AIMS: To evaluate the effects of different sodium-glucose co-transporter 2 (SGLT2) inhibitors on the risk of urinary tract infections (UTIs) and genital infections in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We systematically searched PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to October 9, 2016 to identify randomized controlled trials (RCTs) reporting the occurrence of UTIs and genital infections in patients with T2DM treated with SGLT2 inhibitors...
November 12, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27862160/in-vitro-and-physiologically-based-pharmacokinetic-based-assessment-of-drug-drug-interaction-potential-of-canagliflozin
#20
Rao N V S Mamidi, Shannon Dallas, Carlo Sensenhauser, Heng Keang Lim, Ellen Scheers, Peter Verboven, Filip Cuyckens, Laurent Leclercq, David C Evans, Michael F Kelley, Mark D Johnson, Jan Snoeys
AIMS: Canagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed. METHODS: DDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transporters. Basic predictive approaches were applied to determine potential interactions in vivo. A physiologically-based pharmacokinetic (PBPK) model was developed and clinical DDI simulations were performed to determine the likelihood of cytochrome P450 (CYP) inhibition by canagliflozin...
November 11, 2016: British Journal of Clinical Pharmacology
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