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Dapagliflozin and canagliflozin

Mikhail Kosiborod, Carolyn S P Lam, Shun Kohsaka, Dae Jung Kim, Avraham Karasik, Jonathan Shaw, Navdeep Tangri, Su-Yen Goh, Marcus Thuresson, Hungta Chen, Filip Surmont, Niklas Hammar, Peter Fenici
BACKGROUND: Randomized trials demonstrated lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high CV risk. Prior real-world data suggested similar SGLT-2i effects in T2D patients with broader risk profile, but focused on heart failure and death, and were limited to US and Europe. OBJECTIVES: To examine a broad range of CV outcomes in patients initiated on SGLT-2i vs. other glucose lowering drugs (oGLD) across six countries in Asia Pacific, Middle East and North America (NCT02993614)...
March 7, 2018: Journal of the American College of Cardiology
Rhona Johnston, Olalekan Uthman, Ewen Cummins, Christine Clar, Pamela Royle, Jill Colquitt, Bee Kang Tan, Andrew Clegg, Saran Shantikumar, Rachel Court, J Paul O'Hare, David McGrane, Tim Holt, Norman Waugh
No abstract text is available yet for this article.
February 2018: Health Technology Assessment: HTA
Mahakpreet Singh, Anoop Kumar
Sodium glucose co-transport 2 inhibitors (SGLT2-i) are the new class of anti-diabetic medications which are the recently approved (2013) by FDA for the treatment of diabetes. These inhibitors block the SGLT2 protein which involved in glucose reabsorption from proximal renal tubule which results in increased glucose excretion and lower blood glucose levels. These inhibitors exert favourable effects beyond glucose control such as consistent body weight, blood pressure, and serum uric acid reductions. Canagliflozin, Dapagliflozin, and Empagliflozin belong to the class of SGLT2 inhibitors...
February 25, 2018: Current Drug Safety
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
Charles Khouri, Jean-Luc Cracowski, Matthieu Roustit
OBJECTIVE: Inhibitors of the sodium-glucose co-transporter-2 (SGLT-2) are a novel class of glucose lowering agents showing promising results. However, the use of canagliflozin has been associated with an increased risk of lower-limb amputation. Whether this risk concerns other SGLT-2 inhibitors is unclear. METHODS: We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase®) to address this issue. RESULTS: Among the 8,293,886 reports available between January 2013 and December 2017, we identified 79 reports of lower-limb amputations associated with SGLT-2 inhibitors...
February 12, 2018: Diabetes, Obesity & Metabolism
Konstantinos Avranas, Konstantinos Imprialos, Konstantinos Stavropoulos, Georgios Lales, Alexandos Manafis, Anastasia Skalkou, Lars Kihm
BACKGROUND: The treatment of diabetes remains over the decades challenging, even after the introduction of numerous novel drugs of different classes. Most patients with type 2 diabetes necessitate the combination of multiple agents and eventually use of insulin. The newest, and possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 inhibitors (SGLT-2i). This class has a unique mechanism inhibiting the glucose reabsorption in the proximal tubule of the kidney...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
Cheryl Neslusan, Anna Teschemaker, Michael Willis, Pierre Johansen, Lien Vo
INTRODUCTION: Agents that inhibit sodium glucose co-transporter 2 (SGLT2), including canagliflozin and dapagliflozin, are approved in the United States for the treatment of adults with type 2 diabetes mellitus (T2DM). SGLT2 inhibition lowers blood glucose by increasing urinary glucose excretion, which leads to a mild osmotic diuresis and a net loss of calories that are associated with reductions in body weight and blood pressure. This analysis evaluated the cost-effectiveness of canagliflozin 300 mg versus dapagliflozin 10 mg in patients with T2DM inadequately controlled with metformin in the United States...
February 6, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Muhammad Shariq Usman, Tariq Jamal Siddiqi, Muhammad Mustafa Memon, Muhammad Shahzeb Khan, Wasiq Faraz Rawasia, Muhammad Talha Ayub, Jayakumar Sreenivasan, Yasmeen Golzar
Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors...
January 1, 2018: European Journal of Preventive Cardiology
Alexandros Briasoulis, Omar Al Dhaybi, George L Bakris
PURPOSE OF REVIEW: We sought to review currently available data on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes mellitus patients with hypertension. RECENT FINDINGS: Inhibition of SGLT2 in the renal proximal tubule results in increased urinary glucose excretion and modest improvements of hemoglobin A1C. Treatment with any of the three currently FDA-approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results in sustained systolic and diastolic blood pressure reduction, in part via minimal natriuresis and possible reductions in sympathetic tone...
January 19, 2018: Current Cardiology Reports
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
March 2018: Expert Opinion on Drug Safety
Vishal Gupta, William Canovatchel, B N Lokesh, Ravi Santani, Nishant Garodia
Revelations of the multifactorial pathogenesis of type 2 diabetes mellitus (T2DM) that extend beyond the role of insulin and glucose utilization have been crucial in redefining the treatment paradigm. The focus of treatment is currently directed towards achieving wide-ranging targets encompassing the management of cardiovascular comorbidities that have been evidenced as indispensable aspects of T2DM. While most currently prescribed antihyperglycemic agents have little or no effect on reducing cardiovascular risks, some have been associated with undesirable effects on common risk factors such as weight gain and cardiovascular sequelae...
November 2017: Indian Journal of Endocrinology and Metabolism
Fatima Saleem
Sodium-glucose co-transporter 2 inhibitors (SGLT2is) such as dapagliflozin, canagliflozin, and empagliflozin, are a promising new therapy in the treatment of type 2 diabetes mellitus (T2DM). SGLT2is can effectively reduce hyperglycemia thus improving glycemic control and they offer some beneficial effects on the cardiovascular (CV) system which can benefit patients with heart failure in addition toT2DM. The United States Food and Drug Administration requires new diabetes mellitus therapies to show a CV safety profile...
October 5, 2017: Curēus
Laween Uthman, Antonius Baartscheer, Boris Bleijlevens, Cees A Schumacher, Jan W T Fiolet, Anneke Koeman, Milena Jancev, Markus W Hollmann, Nina C Weber, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) constitute a novel class of glucose-lowering (type 2) kidney-targeted agents. We recently reported that the SGLT2i empagliflozin (EMPA) reduced cardiac cytosolic Na+ ([Na+ ]c ) and cytosolic Ca2+ ([Ca2+ ]c ) concentrations through inhibition of Na+ /H+ exchanger (NHE). Here, we examine (1) whether the SGLT2i dapagliflozin (DAPA) and canagliflozin (CANA) also inhibit NHE and reduce [Na+ ]c ; (2) a structural model for the interaction of SGLT2i to NHE; (3) to what extent SGLT2i affect the haemodynamic and metabolic performance of isolated hearts of healthy mice...
March 2018: Diabetologia
Konstantinos A Toulis, John P Bilezikian, G Neil Thomas, Wasim Hanif, Kalliopi Kotsa, Rasiah Thayakaran, Deepiksana Keerthy, Abd A Tahrani, Krishnarajah Nirantharakumar
An increase in fracture risk has been reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium-glucose co-transporter-2 (SGLT2) inhibitor class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture; therefore, we performed a population-based, open cohort study (from January 2013 to January 2016) using The Health Improvement Network (THIN). A total of 22 618 people with T2DM (4548 exposed to dapagliflozin and 18 070 receiving standard antidiabetic treatment, matched for age, sex, body mass index and diabetes duration) with no history of fractures at baseline were included...
November 30, 2017: Diabetes, Obesity & Metabolism
O Esteban-Jiménez, C Navarro-Pemán, L Urieta-González
OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. MATERIAL AND METHODS: An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. RESULTS: A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26...
January 2018: Semergen
A Perlman, S N Heyman, I Matok, J Stokar, M Muszkat, A Szalat
BACKGROUND AND AIMS: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. METHODS AND RESULTS: We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016...
December 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Xiaoling Cai, Wenjia Yang, Xueying Gao, Yifei Chen, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors. METHODS: Overall, 55 placebo-controlled trials were included. RESULTS: The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1...
January 2018: Obesity
Leyna Leite Santos, Fernando José Camello de Lima, Célio Fernando de Sousa-Rodrigues, Fabiano Timbó Barbosa
INTRODUCTION: Diabetes mellitus is one of the most common chronic diseases in the world, with high morbidity and mortality rates, resulting in a greatly negative socioeconomic impact. Although there are several classes of oral antidiabetic agents, most of the patients are outside the therapeutic goal range. OBJECTIVE: To review the use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus, focusing on their favorable and unfavorable effects, as well as on cardiovascular profile...
July 2017: Revista da Associação Médica Brasileira
Marc Evans, Sayeed Achha, Cheryl Neslusan
INTRODUCTION: Diabetes-related costs make up a large portion of healthcare expenditures in the UK. Many of these costs are related to treatment of diabetes-related complications. Reducing HbA1c to <7.0% (53 mmol/mol) reduces the incidence of complications and comorbidities. Metformin plus sulfonylurea is the most common dual oral combination therapy in the UK. The costs of achieving HbA1c <7.0% in patients inadequately controlled on metformin plus sulfonylurea were analyzed for the sodium glucose co-transporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin from the perspective of the UK National Health System...
October 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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
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