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Saxagliptin

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https://www.readbyqxmd.com/read/29912623/saxagliptin-upregulates-nesfatin-1-secretion-and-ameliorates-insulin-resistance-and-metabolic-profiles-in-type-2-diabetes-mellitus
#1
Kuanlin Chen, Tiejun Zhuo, Jian Wang, Qing Mei
BACKGROUND AND AIMS: Saxagliptin as one of dipeptidyl peptidase-4 (DPP-4) inhibitors can effectively improve glycaemic control in type 2 diabetes mellitus, and nesfatin-1 is regarded as a very important factor in regulating feeding behavior and energy homeostasis. In this trial, we observed the effect of saxagliptin on regulating nesfatin-1 secretion and ameliorating insulin resistance and metabolic profiles in type 2 diabetes mellitus. METHODS: One hundred two type 2 diabetes participants (M/F = 48/54) were investigated...
June 18, 2018: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/29906562/amino-acid-conjugated-chitosan-nanoparticles-for-the-brain-targeting-of-a-model-dipeptidyl-peptidase-4-inhibitor
#2
Jessica Fernandes, M Vivek Ghate, Sanchari Basu Mallik, Shaila A Lewis
Saxagliptin (SAX) is dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-L-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX...
June 12, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29895906/repositioning-of-omarigliptin-as-a-once-weekly-intranasal-anti-parkinsonian-agent
#3
Bassam M Ayoub, Shereen Mowaka, Marwa M Safar, Nermeen Ashoush, Mona G Arafa, Haidy E Michel, Mariam M Tadros, Mohamed M Elmazar, Shaker A Mousa
Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work...
June 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29891647/saxagliptin-prevents-increased-coronary-vascular-stiffness-in-aortic-banded-mini-swine
#4
Bradley S Fleenor, An Ouyang, T Dylan Olver, Jessica A Hiemstra, Melissa S Cobb, Gianmaria Minervini, Craig A Emter
Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin-a DPP-4 inhibitor-on coronary stiffness in aortic-banded mini swine...
June 11, 2018: Hypertension
https://www.readbyqxmd.com/read/29851442/impact-of-formulary-restrictions-on-medication-intensification-in-diabetes-treatment
#5
Bruce C Stuart, Julia F Slejko, Juan-David Rueda, Catherine Cooke, Xian Shen, Pamela Roberto, Michael Ciarametaro, Robert Dubois
OBJECTIVES: To explore formulary restrictions on noninsulin antihyperglycemic drugs (NIADs) in Medicare Part D plans and to estimate the impact of formulary restrictions on use of NIADs among low-income subsidy (LIS) recipient enrollees with type 2 diabetes (T2D) undergoing treatment intensification. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort of 2919 LIS enrollees with T2D receiving metformin monotherapy during the first quarter of 2012 who intensified treatment later in the year was tracked to assess selection of and days' supply with sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and other NIADs...
May 2018: American Journal of Managed Care
https://www.readbyqxmd.com/read/29807374/-diabetes-mellitus-type-2-recent-publications-and-new-drugs
#6
Ulf Elbelt
Since 2013 several placebo-controlled cardiovascular outcomes trails on new classes of glucose-lowering agents in addition to standard care have been reported. These trails were designed to demonstrate non-inferiority to placebo with regard to cardiovascular safety for patients with type 2 diabetes mellitus at high cardiovascular risk.For the glucagon-like peptide 1 (GLP-1)-receptor agonists liraglutide and semaglutide as well as for the sodium-glucose cotransporter-2 (SGLT-2) inhibitors empagliflozin and canagliflozin statistically significant reductions of the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were demonstrated...
June 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29802530/characterization-of-the-open-label-lead-in-period-of-two-randomized-controlled-phase-3-trials-evaluating-dapagliflozin-saxagliptin-and-metformin-in-type-2-diabetes
#7
Chantal Mathieu, Doina Catrinoiu, Aurelian Emil Ranetti, Eva Johnsson, Lars Hansen, Hungta Chen, Ricardo Garcia-Sanchez, Nayyar Iqbal, Aleksander Celiñski
INTRODUCTION: To examine the utility of sequential versus dual add-on approaches in patients who have type 2 diabetes and inadequate glycemic control with metformin therapy alone, we characterized the efficacy and safety of dual therapy with dapagliflozin or saxagliptin added to metformin in the open-label lead-in periods of two phase 3 trials (study 1, NCT01619059; study 2, NCT01646320) that evaluated triple therapy in patients with inadequately controlled type 2 diabetes. METHODS: During the lead-in periods of each trial, patients [glycated hemoglobin (HbA1c) 8...
May 25, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29787616/efficacy-and-safety-of-saxagliptin-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#8
Peng Men, Xiao-Tong Li, Hui-Lin Tang, Suo-di Zhai
OBJECTIVE: To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D). METHODS: A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs)...
2018: PloS One
https://www.readbyqxmd.com/read/29766510/ineffectiveness-of-saxagliptin-as-a-neuroprotective-drug-in-6-ohda-lesioned-rats
#9
Joelle de Melo Turnes, Taysa Bervian Bassani, Leonardo C Souza, Maria A B F Vital
OBJECTIVES: To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. METHODS: Male Wistar rats (weighing 280-300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days...
May 16, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29748970/dipeptidyl-peptidase-4-inhibition-prevents-cell-death-via-extrinsic-and-intrinsic-apoptotic-pathways-in-rat-pancreas-with-insulin-resistance
#10
Gulay Nephan, Zeynep Mine Coskun, Sema Bolkent
The study aims to evaluate the effect of saxagliptin, a specific inhibitor of dipeptidyl peptidase-4 enzymes, on body weight gain, lipid profiles, and cell death through apoptosis in rats with insulin resistance (IR). Male adult Sprague-Dawley rats (n = 32) were divided into 4 groups: control (Ctrl), IR, saxagliptin control, and IR treated with saxagliptin(IR + S). Insulin resistance was induced by 10% fructose in the drinking water for 8 weeks. Saxagliptin (10 mg/kg/day) was administrated by oral gavage for 2 weeks...
June 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29748368/cardiovascular-effects-of-new-oral-glucose-lowering-agents-dpp-4-and-sglt-2-inhibitors
#11
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/29727906/sequential-treatment-escalation-with-dapagliflozin-and-saxagliptin-improves-beta-cell-function-in-type-2-diabetic-patients-on-previous-metformin-treatment-an-exploratory-mechanistic-study
#12
Thomas Forst, Mohammed Khaled Alghdban, Annelie Fischer, Matthias M Weber, Stephan Voswinkel, Tim Heise, Christoph Kapitza, Leona Plum-Mörschel
We investigated the effect of sequential treatment escalation with dapagliflozin and saxagliptin on beta cell function in patients with T2DM insufficiently controlled on metformin monotherapy during a hyperglycaemic clamp investigation. Twenty-six patients (19 males, age 63.5±7.0 years; duration of diabetes 8.8±4.7 years; HbA1c 63.9±15.8 mmol/mol; mean±SD) were enrolled in the study. During a first treatment period (TP1) all patients received 10 mg dapagliflozin for one month, followed by the addition of 5 mg saxagliptin or placebo for another month (TP2)...
May 4, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29724198/the-synergistic-effects-of-saxagliptin-and-metformin-on-cd34-endothelial-progenitor-cells-in-early-type-2-diabetes-patients-a-randomized-clinical-trial
#13
Fiona J Dore, Cleyton C Domingues, Neeki Ahmadi, Nabanita Kundu, Yana Kropotova, Sara Houston, Carol Rouphael, Aytan Mammadova, Linda Witkin, Anamil Khiyami, Richard L Amdur, Sabyasachi Sen
AIMS: Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients. METHODS: In 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg...
May 3, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29682682/molecular-and-clinical-roles-of-incretin-based-drugs-in-patients-with-heart-failure
#14
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...
May 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29679391/cardiovascular-effects-of-sitagliptin-an-anti-diabetes-medicine
#15
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
#16
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...
May 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
#17
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
#18
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
#19
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
#20
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...
April 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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