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Saxagliptin

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https://www.readbyqxmd.com/read/29682682/molecular-and-clinical-roles-of-incretin-based-drugs-in-patients-with-heart-failure
#1
REVIEW
Bassant Orabi, Rasha Kaddoura, Amr S Omar, Cornelia Carr, Abdulaziz Alkhulaifi
Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors produce some beneficial and deleterious effects in diabetic patients not mediated by their glycemic lowering effects, and there is a need for better understanding of the molecular basis of these effects. They possess antioxidant and anti-inflammatory effects with some direct vasodilatory action (animal and human trial data) that may indirectly influence heart failure (HF). Unlike GLP-1R agonists, signaling for HF adverse effects was observed with two DPP-4 inhibitors, saxagliptin and alogliptin...
April 23, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29679391/cardiovascular-effects-of-sitagliptin-an-anti-diabetes-medicine
#2
REVIEW
Yi Zhou, Zhiying Guo, Wenjing Yan, Wen Wang
Dipeptidyl-peptidase-4 (DPP-4) inhibitors, as the most recent available anti-diabetic agents, were generally used in clinical treatment of type 2 diabetes (T2DM). In addition to anti-diabetic effects, the five most widely used DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) also exert cardiovascular protective effects. In recent years, increasing studies suggest that sitagliptin shows pleiotropic impacts towards the cardiovascular system either with or without diabetes...
April 21, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29671284/comparative-cardiovascular-risks-of-dipeptidyl-peptidase-4-inhibitors-analyses-of-real-world-data-in-korea
#3
Kyoung Hwa Ha, Bongseong Kim, Hae Sol Shin, Jinhee Lee, Hansol Choi, Hyeon Chang Kim, Dae Jung Kim
BACKGROUND AND OBJECTIVES: To compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes. METHODS: We identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System...
February 27, 2018: Korean Circulation Journal
https://www.readbyqxmd.com/read/29659121/glucagon-like-peptide-1-ameliorates-cardiac-lipotoxicity-in-diabetic-cardiomyopathy-via-the-ppar%C3%AE-pathway
#4
Lujin Wu, Ke Wang, Wei Wang, Zheng Wen, Peihua Wang, Lei Liu, Dao Wen Wang
Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4 and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high-fat diets were significantly reversed by exendin-4 and saxagliptin treatments for 8 weeks...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29609611/association-between-industry-payments-and-prescribing-costly-medications-an-observational-study-using-open-payments-and-medicare-part-d-data
#5
Manvi Sharma, Aisha Vadhariya, Michael L Johnson, Zachary A Marcum, Holly M Holmes
BACKGROUND: While many new medications may offer advantages over existing drugs, some newer drugs are reformulations of existing products that provide little innovation or incremental benefit while driving up drug costs. Despite the lack of benefit of these medications, prescribers may be motivated by payments made by the pharmaceutical industry. The objective of the study was to determine the association between payments made to physicians by the pharmaceutical industry and prescriptions for certain selected costly brand name drugs...
April 2, 2018: BMC Health Services Research
https://www.readbyqxmd.com/read/29580624/antidiabetic-gliptins-affect-biofilm-formation-by-streptococcus-mutans
#6
Arpan De, Arianna Pompilio, Jenifer Francis, Iain C Sutcliffe, Gary W Black, Giulio Lupidi, Dezemona Petrelli, Luca A Vitali
Streptococcus mutans, a dental caries causing odontopathogen, produces X-prolyl dipeptidyl peptidase (Sm-XPDAP, encoded by pepX), a serine protease known to have a nutritional role. Considering the potential of proteases as therapeutic targets in pathogens, this study was primarily aimed at investigating the role of Sm-XPDAP in contributing to virulence-related traits. Dipeptidyl peptidase (DPP IV), an XPDAP analogous enzyme found in mammalian tissues,is a well known therapeutic target in Type II diabetes. Based on the hypothesis that gliptins, commonly used as anti-human-DPP IV drugs, may affect bacterial growth upon inhibition of Sm-XPDAP, we have determined their ex vivo antimicrobial and anti-biofilm activity towards S...
April 2018: Microbiological Research
https://www.readbyqxmd.com/read/29549573/pharmacovigilance-evaluation-of-the-association-between-dpp-4-inhibitors-and-heart-failure-stimulated-reporting-and-moderation-by-drug-interactions
#7
Gian Paolo Fadini, Mayur Sarangdhar, Angelo Avogaro
INTRODUCTION: In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. METHODS: We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports...
March 16, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29520964/type-2-diabetes-mellitus-and-heart-failure-a-position-statement-from-the-heart-failure-association-of-the-european-society-of-cardiology
#8
REVIEW
Petar M Seferović, Mark C Petrie, Gerasimos S Filippatos, Stefan D Anker, Giuseppe Rosano, Johann Bauersachs, Walter J Paulus, Michel Komajda, Francesco Cosentino, Rudolf A de Boer, Dimitrios Farmakis, Wolfram Doehner, Ekaterini Lambrinou, Yuri Lopatin, Massimo F Piepoli, Michael J Theodorakis, Henrik Wiggers, John Lekakis, Alexandre Mebazaa, Mamas A Mamas, Carsten Tschöpe, Arno W Hoes, Jelena P Seferović, Jennifer Logue, Theresa McDonagh, Jillian P Riley, Ivan Milinković, Marija Polovina, Dirk J van Veldhuisen, Mitja Lainscak, Aldo P Maggioni, Frank Ruschitzka, John J V McMurray
The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice...
March 8, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29518719/quantitative-determination-of-metformin-saxagliptin-and-5-hydroxy-saxagliptin-simultaneously-by-hydrophilic-interaction-liquid-chromatography-electrospray-ionization-mass-spectrometry-and-its-application-to-a-bioequivalence-study-with-a-single-pill-combination
#9
Ying Peng, Qingqing Chang, Na Yang, Shiyin Gu, Yi Zhou, Lifang Yin, Jiye Aa, Guangji Wang, Jianguo Sun
A simple, sensitive and specific hydrophilic interaction liquid chromatography coupled to electrospray ionization mass spectrometric (HILIC-MS) method was developed and validated to determine the plasma concentrations of metformin, saxagliptin and 5-hydroxy saxagliptin simultaneously in clinical studies. Plasma samples were first acidified and then protein precipitated with acetonitrile. Chromatographic separation was achieved on a HILIC Chrom Matrix HP amide column (5 μm, 3.0 × 100 mm I.D.). The mobile phase consisted of acetonitrile and 5 mM ammonium formate buffer containing 0...
February 27, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29516230/the-heart-failure-burden-of-type-2-diabetes-mellitus-a-review-of-pathophysiology-and-interventions
#10
REVIEW
Anne Pernille Ofstad, Dan Atar, Lars Gullestad, Gisle Langslet, Odd Erik Johansen
Diabetes and heart failure (HF) are both global epidemics with tremendous costs on society with increased rates of HF hospitalizations and worsened prognosis when co-existing, making it a significant "deadly duo." The evidence for pharmacological treatment of HF in patients with type 2 diabetes mellitus (T2DM) stems typically from either subgroup analyses of patients that were recruited to randomized controlled trials of HF interventions, usually in patients with reduced ejection fraction (EF), or from subgroup analyses of HF patients recruited to cardiovascular (CV) outcome trials (CVOT) of glucose lowering agents involving patients with T2DM...
March 8, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29508169/combined-sglt2-and-dpp4-inhibition-reduces-the-activation-of-the-nlrp3-asc-inflammasome-and-attenuates-the-development-of-diabetic-nephropathy-in-mice-with-type-2-diabetes
#11
Yochai Birnbaum, Mandeep Bajaj, Hsiu-Chiung Yang, Yumei Ye
BACGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors (DPP4I) are used to treat type 2 diabetes (T2DM). DPP4 inhibitors (DPP4) attenuate Nlrp3 inflammasome activation in the kidney. SGLT2 inhibition reduces inflammation and attenuates the progression of diabetic nephropathy (DN). The effects of dapagliflozin (Dapa) on the activation of the Nlrp3 inflammasome and the combined effect of SGLT2 and DPP4 on T2DM-induced inflammasome activation and progression of DN have not been previously studied...
March 5, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29482528/comparison-of-glycemic-control-and-%C3%AE-cell-function-in-new-onset-t2dm-patients-with-pcos-of-metformin-and-saxagliptin-monotherapy-or-combination-treatment
#12
Tao Tao, Peihong Wu, Yuying Wang, Wei Liu
BACKGROUND: Impaired insulin activity in women with polycystic ovary syndrome might differ from that seen in type 2 diabetes mellitus without polycystic ovary syndrome. This study was designed to compare the effects of treatment with metformin, saxagliptin, and their combination in newly diagnosed women with type 2 diabetes mellitus and polycystic ovary syndrome in China. METHODS: A total of 75 newly diagnosed patients from Shanghai, China with type 2 diabetes mellitus and polycystic ovary syndrome were included in this randomized, parallel, open-label study...
February 27, 2018: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/29468916/the-safety-of-gliptins-updated-data-in-2018
#13
REVIEW
André Jacques Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) are generally considered as glucose-lowering agents with a safe profile in type 2 diabetes. Areas covered: An updated review of recent safety data from randomised controlled trials, observational studies, meta-analyses, pharmacovigilance reports regarding alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin, with a special focus on risks of hypoglycemia, pancreatitis and pancreatic cancer, major cardiovascular events, hospitalisation for heart failure and other new safety issues, such as bone fractures and arthralgia...
April 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29450684/application-and-impact-of-run-in-studies
#14
Michael Fralick, Jerry Avorn, Jessica M Franklin, Abdurrahman Abdurrob, Aaron S Kesselheim
BACKGROUND: A run-in phase is often employed prior to randomization in a clinical trial to exclude non-adherent patients, placebo responders, active drug non-responders, or patients who do not tolerate the active drug. This may impact the generalizability of trial results. OBJECTIVE: To determine if clinical outcomes differed between randomized controlled trials with run-in phases compared with randomized controlled trials of the same medication without run-in phases...
February 15, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29446523/safety-and-tolerability-of-dapagliflozin-saxagliptin-and-metformin-in-combination-post-hoc-analysis-of-concomitant-add-on-versus-sequential-add-on-to-metformin-and-of-triple-versus-dual-therapy-with-metformin
#15
Stefano Del Prato, Julio Rosenstock, Ricardo Garcia-Sanchez, Nayyar Iqbal, Lars Hansen, Eva Johnsson, Hungta Chen, Chantal Mathieu
The safety of triple oral therapy with dapagliflozin plus saxagliptin plus metformin, versus dual therapy with dapagliflozin or saxagliptin plus metformin, was compared in a post hoc analysis of three randomized trials of sequential or concomitant add-on of dapagliflozin and saxagliptin to metformin. In the concomitant add-on trial, patients with type 2 diabetes on stable metformin received dapagliflozin 10 mg/day plus saxagliptin 5 mg/day. In sequential add-on trials, patients on metformin plus either saxagliptin 5 mg/day or dapagliflozin 10 mg/day received add-on dapagliflozin 10 mg/day or saxagliptin 5 mg/day, respectively...
February 15, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29394350/blood-pressure-and-cardiovascular-outcomes-in-patients-with-diabetes-and-high-cardiovascular-risk
#16
Brian A Bergmark, Benjamin M Scirica, Ph Gabriel Steg, Christina L Fanola, Yared Gurmu, Ofri Mosenzon, Avivit Cahn, Itamar Raz, Deepak L Bhatt
Aims: Optimal blood pressure for prevention of cardiovascular (CV) events in patients with Type 2 diabetes mellitus (T2DM) remains uncertain and there is concern for increased risk with low diastolic blood pressure (DBP). This study analysed the association between blood pressure and CV outcomes in high-risk patients with T2DM. Methods and results: Patients with T2DM and elevated CV risk were enrolled in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus-Thrombolysis in Myocardial Infarction 53 trial...
January 31, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29364549/dipeptidyl-peptidase-4-inhibitors-and-heart-failure-exacerbation-in-the-veteran-population-an-observational-study
#17
Michael R Cobretti, Benjamin Bowman, Ted Grabarczyk, Emily Potter
OBJECTIVES: The dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are effective modulators of fasting and postprandial hyperglycemia in patients with type 2 diabetes mellitus (T2DM). In 2013 the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) clinical trial found an increased risk of heart failure exacerbation, as a secondary outcome, among patients treated with saxagliptin. This study examines the safety of DPP-4 inhibitors as a class in T2DM in relation to risk of heart failure exacerbations...
March 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29359260/clinical-impact-of-oral-antidiabetic-medications-in-heart-failure-patients
#18
REVIEW
Alberto Palazzuoli, Elena Ceccarelli, Gaetano Ruocco, Ranuccio Nuti
Heart failure (HF) is a common complication in patients with type 2 diabetes and it is closely associated with high morbidity and mortality rate. The incidence of cardiovascular events in patients with diabetes is related to high levels of glycemia, expressed by increase of HbA1c levels. However, there is little evidence to indicate that glycemic control can reduce the incidence of HF events in this population. Recently, several new antidiabetic drugs have been proposed although the exact clinical impact on heart failure occurrence and deterioration is under debate...
January 23, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29241903/effect-of-dipeptidyl-peptidase-4-inhibitors-on-heart-failure-a-network-meta-analysis
#19
COMPARATIVE STUDY
Wen-Qin Guo, Lang Li, Qiang Su, Wei-Ran Dai, Zi-Liang Ye
BACKGROUND: Previous meta-analyses evaluating the effectiveness of individual dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of heart failure (HF) were limited because of the small number of trials with direct comparisons between two treatments. METHODS: A Bayesian network meta-analysis was performed to investigate the relationship between DPP-4 inhibitors and the risk of HF in patients with type-2 diabetes mellitus. The primary outcome was the occurrence of HF or hospital admission for HF...
December 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29239764/treatment-choices-for-the-glycaemic-management-of-patients-with-type-2-diabetes-and-chronic-kidney-disease-analysis-of-the-sail-patient-linked-dataset
#20
Thinzar Min, Gareth I Davies, Sam Rice, James Chess, Jeffrey W Stephens
AIMS: Chronic kidney disease (CKD) is common in type 2 diabetes and limits the treatment choices for glycaemic control. Our aim was to examine real-world prescribing for managing hyperglycaemia in the presence of CKD. METHODS: The SAIL (Secure Anonymised Information Linkage) databank was used to examine prescribing during the period from the 1st of January to 30th December 2014. CKD was defined as:- none or mild CKD, eGFR ≥60mL/min/1.73m2 ; moderate CKD eGFR <60mL/min/1...
November 23, 2017: Diabetes & Metabolic Syndrome
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