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Canagliflozin

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https://www.readbyqxmd.com/read/29764222/comparative-efficacy-of-once-weekly-semaglutide-and-sglt-2-inhibitors-in-type-2-diabetic-patients-inadequately-controlled-with-metformin-monotherapy-a-systematic-literature-review-and-network-meta-analysis
#1
Rohini Sharma, Lars Wilkinson, Hrvoje Vrazic, Evan Popoff, Sandra Lopes, Steve Kanters, Eric Druyts
OBJECTIVE: Treatment intensification with additional antidiabetic 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 15, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29748368/cardiovascular-effects-of-new-oral-glucose-lowering-agents-dpp-4-and-sglt-2-inhibitors
#2
REVIEW
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
https://www.readbyqxmd.com/read/29735306/renoprotective-effects-of-sodium-glucose-cotransporter-2-inhibitors
#3
REVIEW
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
https://www.readbyqxmd.com/read/29717156/high-basolateral-glucose-increases-sodium-glucose-cotransporter-2-and-reduces-sirtuin-1-in-renal-tubules-through-glucose-transporter-2-detection
#4
Hiroyuki Umino, Kazuhiro Hasegawa, Hitoshi Minakuchi, Hirokazu Muraoka, Takahisa Kawaguchi, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+ -dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29704192/sglt2-inhibition-and-heart-failure-current-concepts
#5
REVIEW
Joaquim Silva Custodio, Andre Rodrigues Duraes, Marconi Abreu, Natalia Albuquerque Rocha, Leonardo Roever
Type 2 diabetes mellitus (T2DM) is a major risk factor for several cardiovascular (CV) conditions, including heart failure (HF). However, until recently, no therapy to treat patients with diabetes could also reduce CV risks related to HF. The EMPA-REG OUTCOME trial with empagliflozin was the first to demonstrate significant cardioprotective benefits in this population. Its impressive 35% reduction in hospitalizations for HF drew the attention of the scientific community to the possibility that pharmacologic sodium-glucose cotransporter 2 (SGLT2) inhibition could be part of the armamentarium for treating patients with HF, with and without diabetes...
April 28, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29702499/new-antihyperglycaemic-agents-and-cardiovascular-disease-let-s-be-optimistic
#6
Kalliopi Pafili, Manfredi Rizzo, Nikolaos Papanas
PURPOSE OF REVIEW: Cardiovascular disease (CVD) substantially increases mortality in diabetes mellitus. This narrative review highlights recent research on the putative associations between dipeptyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose co-transporter 2 inhibitors (SGLT-2is) and several cardiovascular risk factors. RECENT FINDINGS: New antihyperglycaemic agents favourably modulate several CVD risk factors, including fasting and postprandial plasma glucose levels, body weight, blood pressure, lipids, microalbuminuria, nonalcoholic fatty liver disease, serum uric acid, and arterial stiffness...
April 26, 2018: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/29695924/cardiovascular-effects-of-sodium-glucose-cotransporter-2-inhibitors
#7
REVIEW
Tricia Santos Cavaiola, Jeremy Pettus
As the first cardiovascular (CV) outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM), the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME® ) trial, which investigated the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL), which compared SGLT2 inhibitors with other classes of glucose-lowering drugs...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/29693360/eligibility-varies-among-the-4-sodium-glucose-cotransporter-2-inhibitor-cardiovascular-outcomes-trials-implications-for-the-general-type-2-diabetes-us-population
#8
Eric T Wittbrodt, James M Eudicone, Kelly F Bell, Devin M Enhoffer, Keith Latham, Jennifer B Green
OBJECTIVES: Guidance to industry from the FDA requires studies to evaluate the cardiovascular safety of novel type 2 diabetes (T2D) medications. Although the objectives of such cardiovascular outcomes trials (CVOTs) are similar, differences in features such as enrollment criteria present a challenge when trying to assess the applicability of these studies to real-world T2D populations. This study evaluated the proportions of US adults with T2D who met the eligibility criteria for each of the 4 sodium-glucose cotransporter-2 (SGLT2) inhibitor CVOTs...
April 2018: American Journal of Managed Care
https://www.readbyqxmd.com/read/29689561/urate-lowering-agents-in-asymptomatic-hyperuricemia-role-of-urine-sediment-analysis-and-musculoskeletal-ultrasound
#9
Davide Viggiano, Giuseppe Gigliotti, Gianfranco Vallone, Anna Giammarino, Michelangelo Nigro, Giovambattista Capasso
Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum...
April 19, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29679303/do-the-sglt-2-inhibitors-offer-more-than-hypoglycemic-activity
#10
REVIEW
Eduardo Flores, Carlos G Santos-Gallego, Nely Diaz-Mejía, Juan Jose Badimon
Type 2 diabetes mellitus (T2DM) is one of the most common chronic health conditions in the USA; it affects approximately 10% of adults with up to one-quarter being undiagnosed. T2DM is associated with substantial cardiovascular (CV) morbidity and mortality. T2DM is a pathological condition characterized by elevated levels of glucose and associated with high CV risk. Traditional hypoglycemic drugs have demonstrated their capability for effective and maintained management of high glucose levels, but they have not significantly impacted on the incidence of CV events...
April 20, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29671627/the-impact-of-non-medical-switch-on-type-2-diabetes-patients-treated-with-canagliflozin-in-the-commercially-insured-us-population
#11
Lawrence Blonde, Chakkarin Burudpakdee, Victoria Divino, Brahim Bookhart, Jennifer Cai, Michael Pfeifer, Craig I Coleman
OBJECTIVE: To assess the impact of non-medical switch (NMS) from canagliflozin on antihyperglycemic agent (AHA) medication taking behavior. METHODS: This retrospective real-world database analysis included patients with type 2 diabetes with a prescription claim for canagliflozin between 8/2015 and 1/2016 using administrative claims and longitudinal prescription data. Patients with NMS from canagliflozin were identified as those with discontinuation or switch of canagliflozin and enrolled in a pharmacy benefit manager that removed CANA from formulary in 2016...
April 19, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29669938/canagliflozin-triggers-the-fgf23-1-25-dihydroxyvitamin-d-pth-axis-in-healthy-volunteers-in-a-randomized-crossover-study
#12
Jenny E Blau, Viviana Bauman, Ellen M Conway, Paolo Piaggi, Mary F Walter, Elizabeth C Wright, Shanna Bernstein, Amber B Courville, Michael T Collins, Kristina I Rother, Simeon I Taylor
BACKGROUND: Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29667921/glycemic-control-of-type-2-diabetes-mellitus-across-stages-of-renal-impairment-information-for-primary-care-providers
#13
Lili Tong, Sharon Adler
Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and elevates individuals' risk for cardiovascular disease, the leading cause of morbidity and mortality in T2DM. Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications...
April 18, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29650603/top-studies-relevant-to-primary-care-practice
#14
REVIEW
Danielle Perry, Michael R Kolber, Christina Korownyk, Adrienne J Lindblad, Jamil Ramji, Joey Ton, G Michael Allan
OBJECTIVE: To summarize 10 high-quality studies from 2017 that have strong relevance to primary care practice. QUALITY OF EVIDENCE: Study selection involved routine literature surveillance by a group of primary care health professionals. This included screening abstracts of important journals and Evidence Alerts, as well as searching the American College of Physicians Journal Club. MAIN MESSAGE: Topics of the 2017 articles include whether treating subclinical hypothyroidism improves outcomes or symptoms; whether evolocumab reduces cardiovascular disease as well as low-density lipoprotein levels; whether lifestyle interventions reduce medication use in patients with diabetes; whether vitamin D prevents cardiovascular disease, cancer, or upper respiratory tract infections; whether canagliflozin reduces clinical events in patients with diabetes; how corticosteroid injections affect knee osteoarthritis; whether drained abscesses benefit from antibiotic treatment; whether patients with diabetes benefit from bariatric surgery; whether exenatide reduces clinical events in patients with diabetes; and whether tympanostomy tubes affect outcomes in recurrent acute otitis media or chronic otitis media...
April 2018: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/29608898/canagliflozin-protects-against-non-alcoholic-steatohepatitis-in-type-2-diabetic-rats-through-zinc-alpha-2-glycoprotein-up-regulation
#15
Soad L Kabil, Nevertyty M Mahmoud
Elevated blood glucose and insulin resistance are triggering factors for non-alcoholic steatohepatitis (NASH). We investigated the effects of the Sodium Glucose co-Transporter 2 (SGLT2) inhibitor canagliflozin on NASH development in rats with type 2 diabetes mellitus as well as the possible underlying mechanisms and for the first time the effect of canagliflozin on the hepatic zinc-α2-glycoprotein (ZAG) levels. Rats were treated with nicotinamide and streptozotocin to reduce the insulin secretory capacity then fed high fat diet for 8 weeks...
June 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29602791/endogenous-glucose-production-and-hormonal-changes-in-response-to-canagliflozin-and-liraglutide-combination-therapy
#16
Robert Martinez, Hussein Al-Jobori, Ali M Ali, John Adams, Muhammad Abdul-Ghani, Curtis Triplitt, Ralph DeFronzo, Eugenio Cersosimo
The decrement in plasma glucose concentration with SGLT2i is blunted by a rise in endogenous glucose production (EGP). We investigated the ability of incretin treatment to offset the EGP increase. T2DM (n=36) subjects were randomized to: (i) CANAgliflozin (ii) LIRAglutide (iii) CANA/LIRA. EGP was measured with 3-3 H-glucose with/without drug for 360 minutes. In the pre-treatment studies EGP (mg/kg•min) was comparable and decreased (2.2±0.1 to 1.7±0.2) during 300-360 minute period (p<0.01). The decrement in EGP was attenuated with CANA (2...
March 30, 2018: Diabetes
https://www.readbyqxmd.com/read/29595326/a-real-world-analysis-of-glycemic-control-among-patients-with-type-2-diabetes-treated-with-canagliflozin-versus-dapagliflozin
#17
Lawrence Blonde, Charmi Patel, Brahim Bookhart, Michael Pfeifer, Yen-Wen Chen, Bingcao Wu
OBJECTIVE: This US retrospective cohort study compared the real-world effectiveness of canagliflozin 300 mg versus dapagliflozin 10 mg on HbA1c reduction in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients initiated on canagliflozin 300 mg or dapagliflozin 10 mg were identified from de-identified claims data in the Optum Clinformatics® database (1/1/2014-9/30/2016). Propensity score matching was used to create balanced cohorts. The primary outcome was proportion of patients with HbA1c <8...
March 29, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29588466/canagliflozin-inhibits-interleukin-1%C3%AE-stimulated-cytokine-and-chemokine-secretion-in-vascular-endothelial-cells-by-amp-activated-protein-kinase-dependent-and-independent-mechanisms
#18
Sarah J Mancini, Daria Boyd, Omar J Katwan, Anastasiya Strembitska, Tarek A Almabrouk, Simon Kennedy, Timothy M Palmer, Ian P Salt
Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29580579/new-glucose-lowering-agents-for-diabetic-kidney-disease
#19
REVIEW
Lisanne C de Vos, Thushan S Hettige, Mark E Cooper
The prevalence of diabetes mellitus is increasing and is associated with a range of complications including nephropathy. New antidiabetic agents are sought which also have positive effects to diminish diabetic complications. Examples of promising new classes of such agents are glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. In addition to cardiovascular protective effects such as weight loss and decreased blood pressure of some of these agents, there is evidence for renoprotective effects with these agents...
March 2018: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29573118/sglt2-inhibitors-and-stroke-risk-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#20
Man Guo, Jingya Ding, Jingsong Li, Jiying Wang, Ting Zhang, Cuiping Liu, Wei Huang, Yang Long, Chenlin Gao, Yong Xu
The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke risk have not been conclusively established. Therefore, we conducted a meta-analysis to evaluate the effects of SGLT2 inhibitors on stroke risk for patients with type 2 diabetes mellitus (T2DM) by searching available randomized trials published on the PubMed, Embase, CENTRAL, Web of Science, Scopus, and ClinicalTrials.gov databases. We identified 32 eligible trials enrolling 75,540 participants. The stroke incidence in groups receiving SGLT2 inhibitor monotherapy or combination therapy did not significantly differ from that in control groups, with relative risk (RR)=1...
March 23, 2018: Diabetes, Obesity & Metabolism
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