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Saxagliptin

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https://www.readbyqxmd.com/read/28984487/dapagliflozin-and-saxagliptin-tablets-for-adults-with-type-2-diabetes
#1
André J Scheen
Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly)...
October 6, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28977602/dipeptidyl-peptidase-4-inhibition-with-saxagliptin-ameliorates-angiotensin-ii-induced-cardiac-diastolic-dysfunction-in-male-mice
#2
Scott M Brown, Cassandra E Smith, Alex I Meuth, Maloree Khan, Annayya R Aroor, Hannah M Cleeton, Gerald A Meininger, James R Sowers, Vincent G DeMarco, Bysani Chandrasekar, Ravi Nistala, Shawn B Bender
Activation of the renin-angiotensin-aldosterone system is common in hypertension and obesity and contributes to cardiac diastolic dysfunction, a condition for which no treatment currently exists. In light of recent reports that antihyperglycemia incretin enhancing dipeptidyl peptidase (DPP)-4 inhibitors exert cardioprotective effects, we examined the hypothesis that DPP-4 inhibition with saxagliptin (Saxa) attenuates angiotensin II (Ang II)-induced cardiac diastolic dysfunction. Male C57BL/6J mice were infused with either Ang II (500 ng/kg/min) or vehicle for 3 weeks receiving either Saxa (10 mg/kg/d) or placebo during the final 2 weeks...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28966696/comparing-adoption-of-breakthrough-and-me-too-drugs-among-medicare-beneficiaries-a-case-study-of-dipeptidyl-peptidase-4-inhibitors
#3
Inmaculada Hernandez, Yuting Zhang
PURPOSE: "Me-too" drugs are new pharmaceuticals with the mechanism of action of an existing drug and are considered less innovative than breakthrough drugs. The objective of this study was to evaluate whether the adoption patterns of the breakthrough drug sitagliptin and the "me-too" drug saxagliptin differed; and to assess whether the patterns differed between Medicare stand-alone (PDP) and Medicare-Advantage Part D (MA-PD) plans. METHODS: Pharmacy claims from a 5% random sample of Medicare Part D beneficiaries were used to identify all prescriptions filled for sitagliptin (breakthrough drug) and saxagliptin ("me-too" drug) between October 1, 2006 and December 31, 2011...
June 2017: Journal of Pharmaceutical Innovation
https://www.readbyqxmd.com/read/28948519/the-use-of-saxagliptin-in-people-with-type-2-diabetes-in-france-the-diapazon-epidemiological-study
#4
Beverley Balkau, Bernard Charbonnel, Alfred Penfornis, Nora Chraibi, Amir Lahouegue, Céline Faure, Florence Thomas-Delecourt, Bruno Detournay
INTRODUCTION: Saxagliptin is a potent, reversible inhibitor of dipeptidyl peptidase-4 that is indicated for the treatment of type 2 diabetes. The DIAPAZON study was a multicenter observational study intended to document the effectiveness, safety and patterns of saxagliptin use in France, including the saxagliptin retention rate, over 2 years of follow-up. METHODS: A geographically representative sample of 304 French physicians (general practitioners and specialist endocrinologists or diabetologists) recruited 1131 adults with type 2 diabetes into an ambispective cohort; 1033 fulfilled the inclusion criteria...
September 25, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28932239/computational-analysis-of-gynura-bicolor-bioactive-compounds-as-dipeptidyl-peptidase-iv-inhibitor
#5
Lina Rozano, Muhammad Redha Abdullah Zawawi, Muhamad Aizuddin Ahmad, Indu Bala Jaganath
The inhibition of dipeptidyl peptidase-IV (DPPIV) is a popular route for the treatment of type-2 diabetes. Commercially available gliptin-based drugs such as sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin were specifically developed as DPPIV inhibitors for diabetic patients. The use of Gynura bicolor in treating diabetes had been reported in various in vitro experiments. However, an understanding of the inhibitory actions of G. bicolor bioactive compounds on DPPIV is still lacking and this may provide crucial information for the development of more potent and natural sources of DPPIV inhibitors...
2017: Advances in Bioinformatics
https://www.readbyqxmd.com/read/28926170/efficacy-and-safety-of-saxagliptin-in-combination-with-metformin-as-initial-therapy-in-chinese-patients-with-type-2-diabetes-results-from-the-start-study-a-multicenter-randomized-double-blind-active-controlled-phase-3-trial
#6
Jingtao Dou, Jianhua Ma, Jun Liu, Changjiang Wang, Eva Johnsson, Hui Yao, June Zhao, Changyu Pan
OBJECTIVE: To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycemic control (HbA1c 8.0-12.0%). RESEARCH DESIGN AND METHODS: In this multicenter, double-blind, active-controlled study (The START study: NCT02273050), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo, or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/day over 8 weeks...
September 19, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28903775/nonclinical-and-clinical-pharmacology-evidence-for-cardiovascular-safety-of-saxagliptin
#7
REVIEW
Pia S Pollack, Kristina D Chadwick, David M Smith, Martin Billger, Boaz Hirshberg, Nayyar Iqbal, David W Boulton
BACKGROUND: In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial in patients with type 2 diabetes mellitus (T2D) at high risk of cardiovascular (CV) disease, saxagliptin did not increase the risk for major CV adverse events. However, there was an unexpected imbalance in events of hospitalization for heart failure (hHF), one of six components of the secondary CV composite endpoint, with a greater number of events observed with saxagliptin...
September 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28901796/efficacy-and-safety-of-saxagliptin-in-combination-with-insulin-in-japanese-patients-with-type-2-diabetes-mellitus-a-16-week-double-blind-randomized-controlled-trial-with-a-36-week-open-label-extension
#8
Takashi Kadowaki, Satsuki Muto, Yoshiumi Ouchi, Ryutaro Shimazaki, Yutaka Seino
BACKGROUND: We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint...
October 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#9
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28884600/dapagliflozin-saxagliptin-fixed-dose-tablets-a-new-sodium-glucose-cotransporter-2-and-dipeptidyl-peptidase-4-combination-for-the-treatment-of-type-2-diabetes
#10
Valerie Azzopardi Coppenrath, Tasmina Hydery
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) tablets. DATA SOURCES: Searches of MEDLINE (1946 to July 1, 2017) were conducted using the keywords QTERN, saxagliptin, and dapagliflozin. Additional data were obtained from the prescribing information, the product dossier, and Clinicaltrials.gov . STUDY SELECTION AND DATA EXTRACTION: All English language articles related to pharmacology, pharmacokinetics, efficacy, or safety of the combination therapy in human subjects were reviewed...
September 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28881791/dipeptidyl-peptidase-4-inhibitor-use-is-associated-with-a-lower-risk-of-incident-acute-kidney-injury-in-patients-with-diabetes
#11
Chia-Ter Chao, Jui Wang, Hon-Yen Wu, Kuo-Liong Chien, Kuan-Yu Hung
OBJECTIVES: Dipeptidyl peptidase 4 inhibitor (DPP4i) use potentially slows the progression of diabetic kidney disease, but its effects on the risk of acute kidney injury (AKI) are unclear. We aimed to assess the association between DPP4i use and incident AKI episodes from a nationally representative cohort in Taiwan. MATERIALS AND METHODS: All patients newly diagnosed with diabetes mellitus (DM) between 2008, when DPP4i use was first approved in Taiwan, and mid-2013 were enrolled...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878934/postauthorization-safety-study-of-the-dpp-4-inhibitor-saxagliptin-a-large-scale-multinational-family-of-cohort-studies-of-five-outcomes
#12
Vincent Lo Re, Dena M Carbonari, M Elle Saine, Craig W Newcomb, Jason A Roy, Qing Liu, Qufei Wu, Serena Cardillo, Kevin Haynes, Stephen E Kimmel, Peter P Reese, David J Margolis, Andrea J Apter, K Rajender Reddy, Sean Hennessy, Harshvinder Bhullar, Arlene M Gallagher, Daina B Esposito, Brian L Strom
OBJECTIVE: To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. RESEARCH DESIGN AND METHODS: Cohort studies using 2009-2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare)...
2017: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/28859968/dipeptidyl-peptidase-4-independent-cardiac-dysfunction-links-saxagliptin-to-heart-failure
#13
Chintan N Koyani, Ewald Kolesnik, Gerald Wölkart, Niroj Shrestha, Susanne Scheruebel, Christopher Trummer, Klaus Zorn-Pauly, Astrid Hammer, Petra Lang, Helga Reicher, Heinrich Maechler, Klaus Groschner, Bernd Mayer, Peter P Rainer, Harald Sourij, Wolfgang Sattler, Ernst Malle, Brigitte Pelzmann, Dirk von Lewinski
Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca(2+)/calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca(2+)-ATPase 2a axis and Na(+)-Ca(2+) exchanger function in Ca(2+) extrusion...
August 30, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28844525/oral-antidiabetic-agents-and-cardiovascular-outcomes
#14
Manan Pareek, Deepak L Bhatt
Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes; however, a direct protective effect of tight glycemic control remains unproven. In fact, until 2008, when concerns related to rosiglitazone prompted regulatory agencies to mandate assessment of cardiovascular safety of new antidiabetic agents, little was known about how these medications affected cardiovascular outcomes. Since then, there has been a considerable increase in the number of cardiovascular trials, which employ a noninferiority design and focus on high-risk populations to establish safety in the shortest time possible...
July 29, 2017: Current Problems in Cardiology
https://www.readbyqxmd.com/read/28832656/involvement-of-insulin-resistance-in-d-galactose-induced-age-related-dementia-in-rats-protective-role-of-metformin-and-saxagliptin
#15
Sara Kenawy, Rehab Hegazy, Azza Hassan, Siham El-Shenawy, Nawal Gomaa, Hala Zaki, Amina Attia
Age-related dementia is one of the most devastating disorders affecting the elderly. Recently, emerging data suggest that impaired insulin signaling is the major contributor in the development of Alzheimer's dementia (AD), which is the most common type of senile dementia. In the present study, we investigated the potential therapeutic effects of metformin (Met) and saxagliptin (Saxa), as insulin sensitizing agents, in a rat model of brain aging and AD using D-galactose (D-gal, 150 mg/kg/day, s.c. for 90 successive days)...
2017: PloS One
https://www.readbyqxmd.com/read/28827024/gastrointestinal-adverse-events-of-dipeptidyl-peptidase-4-inhibitors-in-type-2-diabetes-a-systematic-review-and-network-meta-analysis
#16
Shanshan Wu, Sanbao Chai, Jun Yang, Ting Cai, Yang Xu, Zhirong Yang, Yuan Zhang, Linong Ji, Feng Sun, Siyan Zhan
PURPOSE: The purpose of this study was to systematically evaluate the effect of dipeptidyl peptidase 4 inhibitors on gastrointestinal adverse events in patients with type 2 diabetes. METHODS: MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from inception through April 28, 2016. Randomized controlled trials that compared dipeptidyl peptidase 4 inhibitor-based therapies with placebo and other hypoglycemic agents in type 2 diabetes were included...
August 18, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28769579/emerging-use-of-combination-therapies-for-the-management-of-type-2-diabetes-focus-on-saxagliptin-and-dapagliflozin
#17
REVIEW
Huan Yu, Vincent C Woo
AIMS: The aim of this article is to review the safety and efficacy data of dapagliflozin, saxagliptin, and their combination in the management of patients with type 2 diabetes. Evidence for the use of the single-tablet combination formulation is also presented. METHODS: A nonsystematic literature review was performed using the Ovid, PubMed, and Google Scholar databases. RESULTS: The addition of dapagliflozin/saxagliptin to metformin can lower mean hemoglobin A1c by as much as 1...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28736981/ketoacidosis-associated-with-sglt2-inhibitor-treatment-analysis-of-faers-data
#18
Jenny E Blau, Sri Harsha Tella, Simeon I Taylor, Kristina I Rother
BACKGROUND: Regulatory agencies have concluded that sodium glucose cotransporter 2 (SGLT2) inhibitors lead to ketoacidosis, but published literature on this point remains controversial. METHODS: We searched the FDA Adverse Event Reporting System (FAERS) for reports of acidosis in patients treated with canagliflozin, dapagliflozin, or empagliflozin (from the date of each drug's FDA approval until May 15, 2015). We compared the number of SGLT2 inhibitor-related reports to reports of acidosis in patients treated with the 2 most commonly used DPP4 inhibitors: sitagliptin and saxagliptin...
July 24, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28671793/-gliptin-gliflozin-combination-for-treating-type-2-diabetes
#19
André J Scheen, Nicolas Paquot
Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycaemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach because the two drugs exert different and potentially complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin...
August 24, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28622738/assessment-of-the-risk-of-hospitalization-for-heart-failure-with-dipeptidyl-peptidase-4-inhibitors-saxagliptin-alogliptin-and-sitagliptin-in-patients-with-type-2-diabetes-using-an-alternative-measure-to-the-hazard-ratio
#20
Masayuki Kaneko, Mamoru Narukawa
BACKGROUND: Saxagliptin statistically significantly increased the risk of hospitalization for heart failure compared with placebo in the clinical trial of SAVOR-TIMI 53. Neither the reason why only saxagliptin among several dipeptidyl peptidase-4 (DPP-4) inhibitors increased the risk, nor the clinical implication of the result has been explained. OBJECTIVE: To evaluate the risk of hospitalization for heart failure associated with DPP-4 inhibitors by using an alternative measure to the hazard ratio...
July 2017: Annals of Pharmacotherapy
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