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https://www.readbyqxmd.com/read/29346597/exenatide-increases-il-1ra-concentration-and-induces-nrf-2-keap-1-regulated-anti-oxidant-enzymes-relevance-to-%C3%AE-cell-function
#1
Paresh Dandona, Husam Ghanim, Sanaa Abuaysheh, Kelly Green, Sandeep Dhindsa, Antoine Makdissi, Manav Batra, Nitesh D Kuhadiya, Ajay Chaudhuri
Purpose: We have previously demonstrated anti-inflammatory and antioxidant effects of exenatide. We have now hypothesized that exenatide also increases the plasma concentration of IL-1RA, an endogenous anti-inflammatory protein and modulates the Nrf-2-Keap-1-ARE system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress. Methods: Twenty four obese type 2 diabetic patients on combined oral and insulin therapy were randomized to receive either exenatide 10μg or placebo b...
January 15, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29341461/effect-of-immediate-and-prolonged-glp-1-receptor-agonist-administration-on-uric-acid-and-its-kidney-clearance-post-hoc-analyses-of-four-clinical-trials
#2
Lennart Tonneijck, Marcel H A Muskiet, Mark M Smits, Petter Bjornstad, Mark H H Kramer, Michaela Diamant, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
AIMS: To determine effects of glucagon-like peptide (GLP)-1 receptor agonists (RA) on uric acid (UA)-levels and kidney UA-clearance. MATERIAL AND METHODS: Post-hoc analyses of four controlled clinical trials, which assessed actions of GLP-1RA-administration on kidney physiology. Immediate effects of GLP-1RA exenatide-infusion versus placebo was determined in 9 healthy overweight males (Study-A) and in 52 overweight T2DM-patients (Study-B). Effects were also examined of 12-week long-acting GLP-1RA liraglutide versus placebo in 36 overweight T2DM-patients (Study-C) and of 8-week short-acting GLP-1RA lixisenatide versus once-daily titrated insulin-glulisine in 35 overweight T2DM-patients (Study-D)...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29341370/real-world-clinical-outcomes-and-predictors-of-glycaemic-and-weight-response-to-exenatide-once-weekly-in-patients-with-type-2-diabetes-the-cibeles-project
#3
Juan José Gorgojo-Martínez, Manuel Angel Gargallo-Fernández, Miguel Brito-Sanfiel, Arturo Lisbona-Catalán
AIMS: To evaluate in a real-world setting the effectiveness of exenatide once-weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and weight response to this drug at 6 months. METHODS: Observational, retrospective, multicenter study in adult patients with T2D and BMI ≥30 kg/m2 from 4 tertiary Spanish hospitals who started ExQW therapy at least 6 months before the inclusion and had not achieved adequate glycaemic control on oral therapies or other GLP-1 receptor agonists...
January 17, 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29335533/fc-modified-exenatide-loaded-nanoparticles-for-oral-delivery-to-improve-hypoglycemic-effects-in-mice
#4
Yanan Shi, Xinfeng Sun, Liping Zhang, Kaoxiang Sun, Keke Li, Youxin Li, Qiang Zhang
To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc was approximately 30 nm larger than that of the unmodified NPs with polydispersity indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest encapsulation efficiency of exenatide in the NPs was greater than 80%...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#5
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29331730/exenatide-exerts-cognitive-effects-by-modulating-the-bdnf-trkb-neurotrophic-axis-in-adult-mice
#6
Manuela Bomba, Alberto Granzotto, Vanessa Castelli, Noemi Massetti, Elena Silvestri, Lorella M T Canzoniero, Annamaria Cimini, Stefano L Sensi
Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration...
December 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29318537/glucose-control-and-weight-change-associated-with-treatment-with-exenatide-compared-with-basal-insulin-a%C3%A2-retrospective-study
#7
Christopher Ll Morgan, Qing Qiao, Susan Grandy, Kristina Johnsson, Sara Jenkins-Jones, Sarah Holden, Craig J Currie
INTRODUCTION: The aim of the study was to compare glycemic and weight change outcomes for type 2 diabetes patients treated with either exenatide once-weekly (EQW) or exenatide twice-daily (EBID) with those patients treated with basal insulin (BI). METHODS: Retrospective data (2010-2014) were extracted from the Clinical Practice Research Datalink, a UK primary care database. Patients previously naïve to injectable therapy initiating EQW, EBID, or BI were extracted and matched by propensity score within two analyses (EQW vs BI and EBID vs BI)...
January 9, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29316164/effects-of-exenatide-once-weekly-plus-dapagliflozin-exenatide-once-weekly-or-dapagliflozin-added-to-metformin-monotherapy-on-body-weight-systolic-blood-pressure-and-triglycerides-in-patients-with-type-2-diabetes-in-the-duration-8-study
#8
Serge A Jabbour, Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Peter Öhman
This post hoc analysis assessed the effects on cardiovascular risk factors of body weight, systolic blood pressure (SBP), and triglycerides after 28 weeks' treatment with exenatide once weekly (QW) plus dapagliflozin, as compared with exenatide QW or dapagliflozin, in patient subpopulations from the DURATION-8 trial of patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. Subgroups of patients were stratified according to their baseline body weight, SBP, and triglycerides...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29301824/clinical-impact-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-uncontrolled-type-2-diabetes-and-very-high-baseline-hba1c-the-freedom-1-hbl-study
#9
Robert R Henry, Julio Rosenstock, Douglas S Denham, Prakash Prabhakar, Lise Kjems, Michelle A Baron
OBJECTIVE: ITCA 650 is a subdermal osmotic mini-pump that continuously delivers exenatide subcutaneously for 3-6 months. The efficacy, safety, and tolerability of ITCA 650 added to diet and exercise alone or combined with metformin, sulfonylurea, or thiazolidinedione monotherapy or a combination of these drugs was evaluated in poorly controlled patients with type 2 diabetes (T2D) who were ineligible for participation in a placebo-controlled study (FREEDOM-1) because of severe hyperglycemia (HbA1c >10% [86 mmol/mol])...
January 4, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29286061/cardioprotection-by-exenatide-a-novel-mechanism-via-improving-mitochondrial-function-involving-the-glp-1-receptor-camp-pka-pathway
#10
Guanglei Chang, Jian Liu, Shu Qin, Youqin Jiang, Peng Zhang, Hui Yu, Kai Lu, Nan Zhang, Li Cao, Ying Wang, Yong Li, Dongying Zhang
Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) and its analogues exert cardioprotective effects via modulating cardiomyocyte metabolism. Mitochondria play a pivotal role in the regulation of cell metabolism. It was hypothesized that treatment with exenatide, a GLP-1 analogue, may exert cardioprotective effects by improving mitochondrial function in an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed to establish an in vitro model of H/R. Exenatide was added to the cells for 30 min prior to exposure to hypoxia...
December 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29283509/exenatide-exhibits-anti-inflammatory-properties-and-modulates-endothelial-response-to-tumor-necrosis-factor-%C3%AE-mediated-activation
#11
Wojciech Garczorz, Enrique Gallego-Colon, Agnieszka Kosowska, Agnieszka Kłych-Ratuszny, Michał Woźniak, Wiesław Marcol, K J Niesner, Tomasz Francuz
INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in the industrialized world. Incretin mimetic compounds such as exenatide are currently used in the treatment of type 2 diabetes. AIMS: We investigated the effects of incretin drugs on apoptosis, adhesion molecule expression, and concentration of extracellular matrix (ECM) metalloproteinases under inflammatory conditions within the context of atherosclerotic plaque formation of both human coronary artery endothelial cells (hCAECs) and human aortic endothelial cells (hAoECs)...
December 28, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29262286/once-weekly-exenatide-and-cardiovascular-outcomes-in-type-2-diabetes
#12
LETTER
Rury R Holman, M Angelyn Bethel, Adrian F Hernandez
New England Journal of Medicine, Volume 377, Issue 25, Page 2502-2502, December 2017.
December 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29260924/pharmacokinetic-drug-evaluation-of-exenatide-for-the-treatment-of-type-2-diabetes
#13
María Molina Vega, Araceli Muñoz-Garach, Francisco J Tinahones
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor analogs are a group of therapeutic agents which mimic endogenous GLP-1, exerting their effect by the stimulation of the GLP-1 receptor with a wide distribution. Its activation increases insulin releasing dependent on blood glucose levels, suppression of glucagon secretion and a reduction of hepatic glucose output. It delays gastric emptying and increases satiety. Exenatide is the synthetic version of exendin-4, a natural peptide with similar properties to human GLP-1...
December 20, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29259802/the-effect-of-the-glp-1-analogue-exenatide-on-functional-connectivity-within-an-nts-based-network-in-women-with-and-without-obesity
#14
K Coveleskie, L A Kilpatrick, A Gupta, J Stains, L Connolly, J S Labus, C Sanmiguel, E A Mayer
Objective: The differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity. Methods: Following an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo...
December 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29249556/both-classic-gs-camp-pka-creb-and-alternative-gs-camp-pka-p38%C3%AE-creb-signal-pathways-mediate-exenatide-stimulated-expression-of-m2-microglial-markers
#15
Hai-Yun Wu, Xue-Qi Tang, Hao Liu, Xiao-Fang Mao, Yong-Xiang Wang
GLP-1 receptor agonists, exenatide and GLP-1, promoted M2 type polarization in monocytes/macrophages and microglial cells. This study explored the signal basis underlying exenatide-stimulated expression of M2 microglia-specific genes, including the cytoplasmic marker Arg 1, surface marker CD206, and secretion protein marker IL-4. Treatment with exenatide in cultured primary microglial cells concentration dependently stimulated the expression of Arg 1, CD206 and IL-4, but did not significantly alter LPS-stimulated expression of TNF-α, IL-1β and IL-6...
December 12, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29246950/efficacy-and-safety-of-once-weekly-semaglutide-versus-exenatide-er-in-subjects-with-type-2-diabetes-sustain-3-a-56-week-open-label-randomized-clinical-trial
#16
Andrew J Ahmann, Matthew Capehorn, Guillaume Charpentier, Francesco Dotta, Elena Henkel, Ildiko Lingvay, Anders G Holst, Miriam P Annett, Vanita R Aroda
OBJECTIVE: To compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c. with exenatide extended release (ER) 2.0 mg s.c. in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this phase 3a, open-label, parallel-group, randomized controlled trial, 813 subjects with type 2 diabetes taking oral antidiabetic drugs were randomized (1:1) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks. The primary end point was change from baseline in HbA1c at week 56...
December 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29242349/efficacy-and-safety-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-type-2-diabetes-uncontrolled-with-oral-antidiabetes-drugs-the-freedom-1-trial
#17
Julio Rosenstock, John B Buse, Rehan Azeem, Prakash Prabhakar, Lise Kjems, Holly Huang, Michelle A Baron
OBJECTIVE: ITCA 650 (exenatide in osmotic mini-pump) continuously delivers exenatide subcutaneously for 3-6 months. Two doses of ITCA 650 were compared with placebo in patients with uncontrolled type 2 diabetes. RESEARCH DESIGN AND METHODS: This 39-week, phase 3, double-blind, placebo-controlled trial randomized 460 patients aged 18-80 years with glycated hemoglobin (HbA1c) 7.5-10% [58-86 mmol/mol] 1:1:1 to placebo, ITCA 650 40 μg/day, or ITCA 650 60 μg/day. Primary end point was change in HbA1c at 39 weeks...
December 14, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29236222/an-indirect-comparison-of-changes-in-the-impact-of-weight-on-quality-of-life-among-subjects-with-type-2-diabetes-treated-with-antihyperglycemic-agents-in-dual-therapy-with-metformin
#18
Shana B Traina, April Slee, Suzy Van Sanden, Joris Diels
INTRODUCTION: It is important to capture the patient experience with a diabetes treatment in clinical trials; however, use of instruments to assess patient-reported outcomes (PROs) in diabetes trials is inconsistent and results may not be reported alongside primary efficacy data. In lieu of head-to-head data, indirect comparisons can be used to compare competing interventions. In this study, we used indirect comparison methods to assess differences in PRO score changes between canagliflozin and other antihyperglycemic agents as add-on to metformin...
December 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29235598/the-stimulation-of-glp-1-secretion-and-delivery-of-glp-1-agonists-via-nanostructured-lipid-carriers
#19
Neha Shrestha, Oriane Bouttefeux, Kevin Vanvarenberg, Patrik Lundquist, Juan Cunarro, Sulay Tovar, Georgiy Khodus, Ellen Andersson, Åsa V Keita, Carlos Gonzalez Dieguez, Per Artursson, Véronique Préat, Ana Beloqui
Nanoparticulate based drug delivery systems have been extensively studied to efficiently encapsulate and deliver peptides orally. However, most of the existing data mainly focus on the nanoparticles as a drug carrier, but the ability of nanoparticles having a biological effect has not been exploited. Herein, we hypothesize that nanostructured lipid carriers (NLCs) could activate the endogenous glucagon-like peptide-1 (GLP-1) secretion and also act as oral delivery systems for GLP-1 analogs (exenatide and liraglutide)...
December 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/29230944/improved-insulin-sensitivity-appears-to-remain-for-a-mean-of-four-years-following-islet-cell-transplant-for-type-1-diabetes
#20
Brett Rydzon, Rebecca S Monson, Jose Oberholzer, Krista A Varady, Melena D Bellin, Kirstie K Danielson
BACKGROUND: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). IS improves shortly after islet cell transplant for type 1 diabetes, yet long-term changes in IS, and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. METHODS: Up to nine years (mean four) of longitudinal data were available on 22 adults (18 female) with T1D who received 1-3 transplants in Phase 1/2 or 3 clinical trials (2004-2014)...
December 12, 2017: Diabetes/metabolism Research and Reviews
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