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Dapagliflozin and canagliflozin

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https://www.readbyqxmd.com/read/28144158/following-the-results-of-the-empa-reg-outcome-trial-with-empagliflozin-is-it-possible-to-speak-of-a-class-effect
#1
Francisco Javier Ampudia-Blasco, Irene Romera, Bernat Ariño, Ramón Gomis
BACKGROUND: The recently published cardiovascular outcomes data for the first sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/28105986/canagliflozin-dapagliflozin-and-empagliflozin-monotherapy-for-treating-type-2-diabetes-systematic-review-and-economic-evaluation
#2
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
BACKGROUND: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors...
January 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28102030/impact-of-sodium-glucose-cotransporter-2-inhibitors-on-nonglycemic-outcomes-in-patients-with-type-2-diabetes
#3
Jennifer M Trujillo, Wesley A Nuffer
The efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin in reducing hyperglycemia in patients with type 2 diabetes is well documented. In addition, positive effects have been observed with these agents on nonglycemic variables, such as reductions in body weight and blood pressure, which may confer additional health benefits. SGLT2 inhibitors are also associated with evidence of renal-protecting benefits. Furthermore, during the landmark Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, a substantial reduction in major adverse cardiovascular outcomes was demonstrated with empagliflozin therapy...
January 19, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28097882/antidiabetic-agents-and-cardiovascular-outcomes-in-patients-with-heart-diseases
#4
Judy W M Cheng, Hisham A Badreldin, Dhiren K Patel, Snehal H Bhatt
This article reviews evidence of benefits and risk of antidiabetic agents in cardiovascular (CV) outcomes, with a focus on medications approved by the FDA since 2008. Peer-reviewed articles were identified from MEDLINE and Current Content database (both 1966 to October 1, 2016) using the search terms insulin, metformin, rosiglitazone, pioglitazone, glyburide, glipizide, glimepiride, acarbose, miglitol, albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide, pramlintide, meglitinide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, colesevalam, bromocriptine, mortality, myocardial infarction (MI), heart failure, (HF) and stroke...
January 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#5
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
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
#6
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
#7
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...
February 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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
#8
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/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: Currently only minimal information is available 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: Thirty-four 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/27867961/cardio-renal-protection-with-empagliflozin
#10
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/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
#11
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/27835680/benefits-and-harms-of-sodium-glucose-co-transporter-2-inhibitors-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#12
Heidi Storgaard, Lise L Gluud, Cathy Bennett, Magnus F Grøndahl, Mikkel B Christensen, Filip K Knop, Tina Vilsbøll
OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND STUDY SELECTION: We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27826881/bone-fractures-with-sodium-glucose-co-transporter-2-inhibitors-how-real-is-the-risk
#13
REVIEW
Edoardo Mannucci, Matteo Monami
This article succinctly summarizes the available evidence on the risk of bone fractures with sodium-glucose co-transporter-2 inhibitors. The US Food and Drug Administration has strengthened the warning for canagliflozin related to the increased risk of bone fractures, and added new information about decreased bone mineral density. The agency has also said that it will evaluate the risk of bone fractures with other drugs in the sodium-glucose co-transporter-2 inhibitor class. Increases in parathyroid hormone levels and decreases in 1,25-dihydroxyvitamin D levels have been postulated as possible mechanisms...
November 8, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/27822054/impact-of-sodium-glucose-cotransporter-2-inhibitors-on-blood-pressure
#14
REVIEW
James W Reed
SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM). These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP) lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin) on BP in patients with T2DM...
2016: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/27689018/the-diabetes-medication-canagliflozin-reduces-cancer-cell-proliferation-by-inhibiting-mitochondrial-complex-i-supported-respiration
#15
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
https://www.readbyqxmd.com/read/27666177/meta-analysis-of-effects-of-sodium-glucose-cotransporter-2-inhibitors-on-cardiovascular-outcomes-and-all-cause-mortality-among-patients-with-type-2-diabetes-mellitus
#16
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 ClinicalTrials.gov 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
https://www.readbyqxmd.com/read/27648101/closing-the-knowledge-gap-on-cardiovascular-disease-in-type-2-diabetes-the-empa-reg-outcome-trial-and-beyond
#17
REVIEW
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
https://www.readbyqxmd.com/read/27628105/elevated-serum-magnesium-associated-with-sglt2-inhibitor-use-in-type-2-diabetes-patients-a-meta-analysis-of-randomised-controlled-trials
#18
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 ClinicalTrials.gov up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels...
December 2016: Diabetologia
https://www.readbyqxmd.com/read/27620988/dapagliflozin-binds-specifically-to-sodium-glucose-cotransporter-2-in-the-proximal-renal-tubule
#19
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
https://www.readbyqxmd.com/read/27604638/physiologically-based-pharmacokinetic-pharmacodynamic-modeling-to-predict-concentrations-and-actions-of-sodium-dependent-glucose-transporter-2-inhibitor-canagliflozin-in-human-intestines-and-renal-tubules
#20
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...
November 2016: Biopharmaceutics & Drug Disposition
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