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Hiroyuki Takashima, Yoshinori Yoshida, Chinami Nagura, Tetsuya Furukawa, Ritsukou Tei, Takashi Maruyama, Noriaki Maruyama, Masanori Abe
BACKGROUND: To evaluate the renoprotective effects of canagliflozin, we assessed the albuminuria-lowering effect in Japanese type 2 diabetes patients with chronic kidney disease (CKD). METHODS: In this prospective, open-label, parallel-group study, type 2 diabetes patients with CKD were randomized to receive either oral canagliflozin (100 mg/day) or usual care (control group) for 52 weeks. Endpoints included changes in urinary albumin-to-creatinine ratio (UACR), other urinary biomarkers, laboratory parameters, and adverse events...
June 1, 2018: Diabetes & Vascular Disease Research
Gallwitz Baptist
Type 2 diabetes (T2D) is associated with numerous comorbidities that significantly reduce quality of life, increase mortality and complicate treatment decisions. In a recent cardiovascular outcomes trial, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin was shown to reduce cardiovascular (CV) mortality and heart failure in high-risk patients with T2D with a previous CV event or with established CV disease (CVD)...
April 2018: European Endocrinology
Eiji Kutoh, Asuka Wada, Teruma Murayama, Jyunka Hayashi
Objectives: The aim of this project is to compare the effect of canagliflozin monotherapy on metabolic parameters between responders and nonresponders with this drug. This study is a prospective, unblinded, observational study. Subjects and Methods: Drug-naïve patients with type 2 diabetes mellitus received only 50-100 mg/day canagliflozin for 3 months ( n = 39). They were divided into two groups according to the novel "A1c index" to assess glycemic efficacies; responders ( n = 24) and nonresponders ( n = 15)...
March 2018: Indian Journal of Endocrinology and Metabolism
Mahmoud El-Daly, Vivek Krishna Pulakazhi Venu, Mahmoud Saifeddine, Koichiro Mihara, Sean Kang, Paul W M Fedak, Laurie A Alston, Simon A Hirota, Hong Ding, Chris R Triggle, Morley D Hollenberg
Hyperglycaemia is a major contributor to diabetic cardiovascular disease with hyperglycaemia-induced endothelial dysfunction recognized as the initiating cause. Coagulation pathway-regulated proteinase-activated receptors (PARs) that can regulate vascular tone in vivo cause eNOS-mediated endothelium-dependent vasodilation; but, the impact of hyperglycaemia on this vasodilatory action of PAR stimulation and the signalling pathways involved are unknown. We hypothesized that vascular sodium-glucose co-transporter 2 activity and hyperglycaemia-induced oxidative stress involving Src-kinase, EGF receptor-kinase, Rho-kinase and protein-kinase-C biochemical signalling pathways would compromise PAR2-mediated endothelium-dependent vasodilation...
June 13, 2018: Vascular Pharmacology
Gordon Sloan, Tania Kakoudaki, Nishant Ranjan
We report a case of a 63-year-old man who developed diabetic ketoacidosis (DKA) associated with canagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor. He presented acutely unwell with a silent myocardial infarction, diverticulitis and DKA with a minimally raised blood glucose level. Standard therapy for DKA was initiated. Despite this, ketonaemia persisted for a total of 12 days after discontinuation of canagliflozin. Glucosuria lasting for several days despite discontinuation of the medications is a recognised phenomenon...
2018: Endocrinology, Diabetes & Metabolism Case Reports
L Das, A Bhansali, R Walia
BACKGROUND: Sodium-glucose co-transporter-2 inhibitors are novel antidiabetes drugs that act via inhibition of renal glucose reabsorption. This action causes osmotic diuresis, reduces intravascular volume and is associated with various adverse effects. In the present paper, we describe the first report on the unmasking of underlying polycythemia vera by canagliflozin in a person with Type 2 diabetes mellitus, which was temporally related to the use of the drug. CASE REPORT: A 51-year-old obese man with Type 2 diabetes was prescribed canagliflozin 100 mg for control of his glycaemia...
June 11, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Akira Mima
AIM: Diabetic kidney disease (DKD) is the most frequent cause of mortality and morbidity, leading a global health burden. This review will focus on the potential therapeutic interventions using Sodium-glucose cotransporter-2 (SGLT2) inhibitors that could prevent the development and progression of DKD. RESULTS: SGLT2 inhibitors have been widely used as anti-diabetic drugs. Recent clinical studies have demonstrated that these drugs, which improve glycemic control and hypertension and decrease body weight, decrease the risk of renal function impairment and heart failure in patients with type 2 diabetes...
May 5, 2018: Journal of Diabetes and its Complications
Ahmed A Abdelsameea, Soad L Kabil
Peripheral nervous system neurotoxicity is the most problematic complication of cisplatin treatment. In this study, we have addressed the possible neuroprotective effect of canagliflozin on cisplatin-induced peripheral neurotoxicity in rats. Rats were randomly allocated into the following: control (vehicle) group, received hydhroxypropyl methyl cellulose; cisplatin group, injected cisplatin 2 mg/kg intraperitoneal, twice a week for 5 consecutive weeks; canagliflozin-cisplatin of received canagliflozin, 10 mg/kg/day by gavage and cisplatin in the same schedule like cisplatin group...
June 3, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
M D Garcia de Lucas, L M Pérez Belmonte, M Suárez Tembra, J Olalla Sierra, R Gómez Huelgas
AIM: To analyze the efficacy and safety of replacing sitagliptin with canagliflozin in patients with type 2 diabetes (T2D) and poor metabolic control despite treatment with sitagliptin in combination with metformin and/or gliclazide. MATERIALS AND METHODS: In this multicentre observational, retrospective, 26-week clinical study of patients with T2D and poor glycaemic control (HbA1c: 7.5-9.5%) treated with sitagliptin in combination with metformin and/or gliclazide, sitagliptin (and gliclazide if appropriate) were replaced by canagliflozin...
May 22, 2018: Diabetes & Metabolism
Dylan Y Ren, Yingmei Zhang
Cardiovascular complications are among the main reasons for the high morbidity and mortality in patients with type 2 diabetes, making the management of cardiovascular complications an integral component in the treatment of type 2 diabetes. Along the same line, the US Food and Drug Administration mandated all new diabetic drugs and therapies have a safe cardiovascular profile. Among various drugs available for the treatment against type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a class of newly developed anti-diabetic agents with properties of mitigating cardiovascular risk in patients with type 2 diabetes...
May 30, 2018: Current Drug Targets
Velen Tat, Christopher P Forest
The sodium glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin represent a novel class of medications to manage type 2 diabetes through urinary excretion of glucose. These drugs block glucose reabsorption by the kidneys to increase glucosuria. These drugs provide hemoglobin A1C reduction, promote weight loss, and remain hypoglycemic-neutral when not used in combination with insulin or secretagogues. Canagliflozin and empagliflozin have shown cardiovascular benefit...
June 2018: JAAPA: Official Journal of the American Academy of Physician Assistants
Ulf Elbelt
Since 2013 several placebo-controlled cardiovascular outcomes trails on new classes of glucose-lowering agents in addition to standard care have been reported. These trails were designed to demonstrate non-inferiority to placebo with regard to cardiovascular safety for patients with type 2 diabetes mellitus at high cardiovascular risk.For the glucagon-like peptide 1 (GLP-1)-receptor agonists liraglutide and semaglutide as well as for the sodium-glucose cotransporter-2 (SGLT-2) inhibitors empagliflozin and canagliflozin statistically significant reductions of the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were demonstrated...
June 2018: Deutsche Medizinische Wochenschrift
Atsushi Tanaka, Koichi Node
Prevention and treatment strategies for heart failure (HF) in diabetes have not been fully established, at least partly due to lack of recognition of a pathological link between the two and effective antidiabetic agents for HF. Recent cardiovascular (CV) outcomes trials demonstrated that treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors greatly improved major CV adverse events in type 2 diabetes (T2D) patients at high risk for CV events, seemingly driven by risk reduction in HF-related outcomes...
May 25, 2018: Cardiovascular Diabetology
Stormi E Gale, Jeannie L Poon, Kristin Watson
Patients with type 2 diabetes mellitus (DM) are known to be at an increased risk for macrovascular complications, and cardiovascular disease (CVD) is one of the greatest drivers of morbidity and mortality in this patient population. Over the past decade, the number of treatment options for type 2 DM has increased. In 2008, the United States Food and Drug Administration mandated an evaluation of cardiovascular (CV) outcomes associated with antihyperglycemic agents. Since that time, the CV risk-benefit profile of many antihyperglycemic treatment modalities have been evaluated; however, results have remained inconsistent...
May 25, 2018: Pharmacotherapy
Nobuya Inagaki, Shin-Ichi Harashima, Hiroaki Iijima
Canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, improves various cardiometabolic parameters. Although canagliflozin was originally discovered in Japan, no comprehensive summary of its effects in Japanese patients has been reported. As differences exist in the pathologic features of diabetes between Japanese and non-Japanese populations, it is important to consolidate Japanese data for canagliflozin. Areas covered: The authors summarize Japanese clinical trial and post-marketing surveillance data for canagliflozin, and make comparisons with non-Japanese data...
May 25, 2018: Expert Opinion on Pharmacotherapy
Daisuke Matsutani, Masaya Sakamoto, Yosuke Kayama, Norihiko Takeda, Ryuzo Horiuchi, Kazunori Utsunomiya
BACKGROUND: Type 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM...
May 22, 2018: Cardiovascular Diabetology
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
Rohini Sharma, Lars Wilkinson, Hrvoje Vrazic, Evan Popoff, Sandra Lopes, Steve Kanters, Eric Druyts
OBJECTIVE: Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin. METHODS: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL...
May 29, 2018: Current Medical Research and Opinion
André J Scheen
Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents...
May 11, 2018: Circulation Research
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
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