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Rong Qiu, Dainius Balis, George Capuano, John Xie, Gary Meininger
: Metformin is typically the first pharmacologic treatment recommended for type 2 diabetes mellitus (T2DM), but many patients do not achieve glycemic control with metformin alone and eventually require combination therapy with other agents. Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was assessed in a comprehensive Phase 3 clinical development program consisting of ~10,000 participants, of which ~80% were on background therapy that consisted of metformin alone or in combination with other antihyperglycemic agents (AHAs; e...
October 12, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Tory J Andrews, Robert D Cox, Christina Parker, James Kolb
BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days...
October 4, 2016: Journal of Emergency Medicine
Linda A Villani, Brennan K Smith, Katarina Marcinko, Rebecca J Ford, Lindsay A Broadfield, Alex E Green, Vanessa P Houde, Paola Muti, Theodoros Tsakiridis, Gregory R Steinberg
OBJECTIVE: The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer cells but the mechanism(s) remain unclear. METHODS: Cellular proliferation and clonogenic survival were used to assess the sensitivity of prostate and lung cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular acidification rate, cellular ATP, glucose uptake, lipogenesis, and phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase, and the p70S6 kinase were assessed...
October 2016: Molecular Metabolism
Huilin Tang, Zhenwei Fang, Tiansheng Wang, Wei Cui, Suodi Zhai, Yiqing Song
The benefit or risk of sodium glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus has not been established. We aimed to assess the comparative CV safety and mortality risk associated with the use of SGLT2 inhibitors. PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and were systematically searched up to January 27, 2016, to identify randomized controlled trials (RCTs) with the use of SGLT2 inhibitors of at least 24 weeks of duration...
August 31, 2016: American Journal of Cardiology
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
Elif A Oral
Type 2 diabetes mellitus (T2DM) is associated with marked cardiovascular (CV) morbidity and mortality, including heart failure (HF). Until recently, an oral glucose-lowering agent that improved hyperglycemia as well as provided CV benefits in patients with T2DM and cardiovascular disease (CVD) was lacking. The newest class of glucose-lowering agents, sodium glucose cotransporter 2 (SGLT2) inhibitors, includes canagliflozin, dapagliflozin, and empagliflozin. Prior to the release of the LEADER trial results, the recent EMPA-REG OUTCOME study was the only dedicated CV trial to demonstrate a reduction in major adverse cardiac events, CV mortality, and all-cause mortality and a reduction in hospitalization for HF with empagliflozin, given on top of standard-of-care therapy in patients with T2DM and CVD...
2016: Drugs in Context
June Felice Johnson, Rahul Parsa, Robert Bailey
OBJECTIVE: To examine characteristics and outcomes of type 2 diabetes (T2DM) patients prescribed canagliflozin (CANA) and managed in the real-world setting of a diabetes clinic. Primary outcome was change in A1c, and secondary outcomes were change in weight and blood pressure. METHODS: Study was an electronic health record (EHR) review of CANA prescribed at the diabetes clinic from June 2013 to June 2015. Patients were included in the study if they were adults with T2DM, received routine follow-up diabetes care at the diabetes clinic, received an initial prescription for CANA from a diabetes clinic prescriber, and returned for at least one follow-up office visit (OV) after initial CANA prescribing...
October 5, 2016: Current Medical Research and Opinion
Jessica Turner, Tahmina Begum, Roger D Smalligan
INTRODUCTION: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are relatively new antihyperglycemic agents that lower renal glucose reabsorption. They are used as adjunctive therapy to standard diabetes treatment. CASE REPORT: We present the case of a 62-year-old woman with a past medical history of type 2 diabetes mellitus and sudden-onset diabetic ketoacidosis (DKA). Use of canagliflozin, a SGLT-2 inhibitor, was determined to be the cause of the DKA. The patient ultimately recovered after 5 days in the intensive care unit...
July 2016: Journal of Investigative Medicine High Impact Case Reports
Maureen Clement, Peter Senior
No abstract text is available yet for this article.
September 2016: Canadian Family Physician Médecin de Famille Canadien
Maureen Clement, Peter Senior
No abstract text is available yet for this article.
September 2016: Canadian Family Physician Médecin de Famille Canadien
Huilin Tang, Xi Zhang, Jingjing Zhang, Yufeng Li, Liana C Del Gobbo, Suodi Zhai, Yiqing Song
AIMS/HYPOTHESIS: By analysing available evidence from randomised controlled trials (RCTs), we aimed to examine whether and to what extent sodium-glucose cotransporter 2 (SGLT2) inhibitors affect serum electrolyte levels in type 2 diabetes patients. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels...
September 15, 2016: Diabetologia
Chiara Ghezzi, Amy S Yu, Bruce A Hirayama, Vladimir Kepe, Jie Liu, Claudio Scafoglio, David R Powell, Sung-Cheng Huang, Nagichettiar Satyamurthy, Jorge R Barrio, Ernest M Wright
Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[(18)F]fluoro-dapagliflozin (F-Dapa)...
September 12, 2016: Journal of the American Society of Nephrology: JASN
Kazumi Mori, Ryuta Saito, Yoshinobu Nakamaru, Makiko Shimizu, Hiroshi Yamazaki
Canagliflozin is a recently developed sodium-glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic-pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized...
September 7, 2016: Biopharmaceutics & Drug Disposition
Mathew John, Sonia Cerdas, Rafael Violante, Chaicharn Deerochanawong, Mohamed Hassanein, April Slee, William Canovatchel, Gill Hamilton
AIMS: Patients with type 2 diabetes mellitus (T2DM) have increased risk of adverse events (AEs; e.g. dehydration, hypoglycaemia) in hot weather. This analysis assessed the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with T2DM who live in hot climates. METHODS: This post hoc analysis evaluated patients with T2DM using pooled data from four 26-week, placebo-controlled studies (N=2,313) and data from a 104-week, active-controlled study (add-on to metformin vs glimepiride; N=1,450)...
September 2016: International Journal of Clinical Practice
Wing Chow, Gavin Miyasato, Fotios K Kokkotos, Robert A Bailey, Erin K Buysman, Henry J Henk
PURPOSE: Randomized controlled trials have found that treatment of type 2 diabetes mellitus with canagliflozin, a sodium glucose co-transporter 2 inhibitor, is associated with significant reductions in glycosylated hemoglobin (HbA1c) levels. However, very few studies have evaluated the effectiveness of sodium glucose co-transporter 2 inhibitors in a real-world context. This data synthesis aims to examine the demographic characteristics and glycemic control among patients treated with canagliflozin in clinical practice, using results obtained from 2 US-specific retrospective administrative claims databases...
September 2016: Clinical Therapeutics
Robert A Bailey, Phil Schwab, Yihua Xu, Margaret Pasquale, Andrew Renda
PURPOSE: Although the efficacy of canagliflozin has been well established in clinical trials, research regarding its use and impact on outcomes in clinical practice has been limited by the availability of data on observations up to and beyond 6 months after the initial use of canagliflozin. The purpose of this study was to evaluate changes in glycemic control after the initiation of canagliflozin use in a managed care population. METHODS: A retrospective cohort analysis in adults with type 2 diabetes mellitus was conducted using medical and pharmacy claims data and laboratory results from the Humana Research Database...
September 2016: Clinical Therapeutics
Nadia M S Arafa, Mohamed-Assem S Marie, Sara Abdullah Mubarak AlAzimi
BACKGROUND: The rapid economic development in the Arabian Gulf has resulted in lifestyle changes that have increased the prevalence of obesity and type 2 diabetes, with the greatest increases observed in Kuwait. Dyslipidemia and diabetes are risk factors for disruptions in cortical neurotransmitter homeostasis. This study investigated the effect of the antidiabetic medications canagliflozin (CAN) and metformin (MET) on the levels of cortical neurotransmitters in a diabetic rat model. MATERIALS AND METHODS: The rats were assigned to the control (C) group, the diabetic group that did not receive treatment (D) or the diabetic group treated with either CAN (10 mg/kg) or MET (100 mg/kg) for 2 or 4 weeks...
October 25, 2016: Chemico-biological Interactions
André J Scheen
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions...
October 2016: Current Diabetes Reports
Hiddo J L Heerspink, Mehul Desai, Meg Jardine, Dainius Balis, Gary Meininger, Vlado Perkovic
Sodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6-8 mg...
August 18, 2016: Journal of the American Society of Nephrology: JASN
Dario Rahelić, Eugen Javor, Tomo Lucijanić, Marko Skelin
Elevated haemoglobin A1c (HbA1c) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence, regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear...
August 18, 2016: Annals of Medicine
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