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Dapagliflozin and canagliflozin

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
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
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
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
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
Matteo Monami, Ilaria Dicembrini, Edoardo Mannucci
AIMS: EMPAREG OUTCOME study showed a reduction in cardiovascular events in patients treated with the sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin, as compared to placebo. Other drugs of the same class are currently been investigated for cardiovascular outcomes. In the meanwhile, a re-analysis of data collected in available studies can add relevant insight. METHODS: A MEDLINE search for SGLT-2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials up to November 16, 2015...
August 4, 2016: Acta Diabetologica
Nellowe Candelario, Jedrzej Wykretowicz
Sodium glucose co-transporter (SGLT-2) inhibitor is a relatively new medication used to treat diabetes. At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class. Risk factors for the development of ketoacidosis among patients who take SGLT-2 inhibitors include decrease carbohydrate intake/starvation, acute illness and decrease in insulin dose...
July 2016: Oxford Medical Case Reports
Hiddo J L Heerspink, Bruce A Perkins, David H Fitchett, Mansoor Husain, David Z I Cherney
Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and natriuretic effects contributing to plasma volume contraction, and decreases in systolic and diastolic blood pressures by 4 to 6 and 1 to 2 mm Hg, respectively, which may underlie cardiovascular and kidney benefits...
September 6, 2016: Circulation
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
Previously we investigated the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan using normal and diabetic mice. We classified the SGLT2 inhibitors with respect to duration of action as either long-acting (ipragliflozin and dapagliflozin) or intermediate-acting (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin). In the present study, antidiabetic effects of repeated administration of these SGLT2 inhibitors in type 2 diabetic mice were investigated...
July 2016: Journal of Pharmacological Sciences
(no author information available yet)
The prevalence of type 2 diabetes is rising, and in 2015 more than 5% of adults in the UK were affected by this condition.(1,2) Management of type 2 diabetes includes encouraging lifestyle changes (increased exercise, modification of diet and smoking cessation) alongside the provision of medication to minimise long-term complications and manage blood sugar control while avoiding unwanted effects of drug treatment.(3) Of particular importance, people with type 2 diabetes are at increased risk of cardiovascular disease, and therefore the aims of treatment also include modification of associated risk factors...
July 2016: Drug and Therapeutics Bulletin
H L Tang, D D Li, J J Zhang, Y H Hsu, T S Wang, S D Zhai, Y Q Song
AIM: To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs)...
July 13, 2016: Diabetes, Obesity & Metabolism
Melanie Davies, Sudesna Chatterjee, Kamlesh Khunti
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin...
2016: Clinical Pharmacology: Advances and Applications
Simon A Hawley, Rebecca J Ford, Brennan K Smith, Graeme J Gowans, Sarah J Mancini, Ryan D Pitt, Emily A Day, Ian P Salt, Gregory R Steinberg, D Grahame Hardie
Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin...
September 2016: Diabetes
Jennifer Cai, Yuexi Wang, Onur Baser, Lin Xie, Wing Chow
OBJECTIVES: Non-adherence and non-persistence to anti-hyperglycemic agents are associated with worse clinical and economic outcomes in patients with type 2 diabetes. This study evaluated treatment persistence and adherence across newer anti-hyperglycemic agents (canagliflozin, dapagliflozin, sitagliptin, saxagliptin, linagliptin, liraglutide, or exenatide). METHODS: This retrospective cohort study of Truven Health Analytics Marketscan databases included adult patients with type 2 diabetes whose first pharmacy claim for a newer anti-hyperglycemic agent was between February 1, 2014 and July 31, 2014...
July 12, 2016: Journal of Medical Economics
Kobi T Nathan, Nabila Ahmed-Sarwar, Paul Werner
OBJECTIVE: To review the chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, dosing, drug interactions, and administration of canagliflozin, dapagliflozin, and empagliflozin, and comparing the benefit and risk aspects of using these agents in the older adult diabetes patient population. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION, AND DATA SYNTHESIS: A search of PubMed using the terms "SGLT-2 inhibitors," "canagliflozin," "dapagliflozin," "empagliflozin," "efficacy," and "tolerability" was performed to find relevant primary literature on each of the sodium/glucose cotransporter 2 (SGLT-2) inhibitors currently approved for use in type 2 diabetes...
May 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
F Zaccardi, D R Webb, Z Z Htike, D Youssef, K Khunti, M J Davies
AIM: To assess the comparative efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors in adults with type 2 diabetes. METHODS: We electronically searched randomized controlled trials (≥24 weeks) including canagliflozin, dapagliflozin or empagliflozin that were published up to 3 November 2015. Data were collected on cardiometabolic and safety outcomes and synthesized using network meta-analyses. RESULTS: A total of 38 trials (23 997 participants) were included...
August 2016: Diabetes, Obesity & Metabolism
Raktim Kumar Ghosh, Dhrubajyoti Bandyopadhyay, Adrija Hajra, Monodeep Biswas, Anjan Gupta
Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago...
June 1, 2016: International Journal of Cardiology
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