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Exenatide ones week

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https://www.readbyqxmd.com/read/28834553/efficacy-of-exenatide-on-weight-loss-metabolic-parameters-and-pregnancy-in-overweight-obese-polycystic-ovary-syndrome
#1
Xin Liu, Ying Zhang, Si-Yuan Zheng, Rong Lin, Yi-Juan Xie, Hui Chen, Yong-Xiong Zheng, En Liu, Lin Chen, Jia-He Yan, Wei Xu, Ting-Ting Mai, Yi Gong
CONTEXT: Weight loss remains one of the most important arms in obese patients with polycystic ovary syndrome (PCOS). Further studies are needed to identify the best treatment. OBJECTIVE: To evaluate the effects of exenatide (EXE) on reproductive and metabolic function in overweight/obese (OW/OB) PCOS. DESIGN: This is a 24-week open-label prospective, randomized, clinical study. PATIENTS AND MEASUREMENTS: This study randomized 176 OW/OB women diagnosed with PCOS to receive either EXE 10 μg BID (n = 88) or metformin (MET) 1000 mg BID (n = 88) for the first 12 weeks...
August 23, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28605180/a-hydrogel-microsphere-drug-delivery-system-that-supports-once-monthly-administration-of-a-glp-1-receptor-agonist
#2
Eric L Schneider, Brian R Hearn, Samuel J Pfaff, Ralph Reid, David G Parkes, Niels Vrang, Gary W Ashley, Daniel V Santi
We have developed a chemically controlled very long-acting delivery system to support once-monthly administration of a peptidic GLP-1R agonist. Initially, the prototypical GLP-1R agonist exenatide was covalently attached to hydrogel microspheres by a self-cleaving β-eliminative linker; after subcutaneous injection in rats, the peptide was slowly released into the systemic circulation. However, the short serum exenatide half-life suggested its degradation in the subcutaneous depot. We found that exenatide undergoes deamidation at Asn(28) with an in vitro and in vivo half-life of approximately 2 weeks...
June 29, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28535629/-association-between-sorcs1-rs1416406-and-therapeutic-effect-of-exenatide
#3
L M Zhou, W Xu, X M Yan, M X Y Li, H Liang, J P Weng
Objective: To study the relationship between SORCS1 gene rs1416406 and efficiency of exenatide. Methods: Between August 2010 and August 2012, a hundred and one newly diagnosed patients with type 2 diabetes mellitus (T2DM) were from CONFIDENCE study covering 25 university-affiliated hospitals in 13 provinces of China. All patients received exenatide treatment for 48 weeks. Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), body mass index (BMI), oral glucose tolerance test (OGTT) glucose and insulin levels were measured before and after therapy...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28489279/dipeptidyl-peptidase-dpp-4-inhibitors-and-glucagon-like-peptide-glp-1-analogues-for-prevention-or-delay-of-type-2-diabetes-mellitus-and-its-associated-complications-in-people-at-increased-risk-for-the-development-of-type-2-diabetes-mellitus
#4
REVIEW
Bianca Hemmingsen, David P Sonne, Maria-Inti Metzendorf, Bernd Richter
BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown. OBJECTIVES: To assess the effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these...
May 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28454792/baseline-characteristics-of-patients-enrolled-in-the-exenatide-study-of-cardiovascular-event-lowering-exscel
#5
RANDOMIZED CONTROLLED TRIAL
Robert J Mentz, M Angelyn Bethel, Stephanie Gustavson, Vivian P Thompson, Neha J Pagidipati, John B Buse, Juliana C Chan, Nayyar Iqbal, Aldo P Maggioni, Steve P Marso, Peter Ohman, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez, Rury R Holman
BACKGROUND: EXSCEL is a randomized, double-blind, placebo-controlled trial examining the effect of exenatide once-weekly (EQW) versus placebo on time to the primary composite outcome (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in patients with type 2 diabetes mellitus (DM) and a wide range of cardiovascular (CV) risk. METHODS: Patients were enrolled at 688 sites in 35 countries. We describe their baseline characteristics according to prior CV event status and compare patients with those enrolled in prior glucagon-like peptide-1 receptor agonist (GLP-1RA) outcomes trials...
May 2017: American Heart Journal
https://www.readbyqxmd.com/read/28435305/glucagon-like-peptide-1-receptor-agonists-a-systematic-review-of-comparative-effectiveness-research
#6
REVIEW
Philip A Levin, Hiep Nguyen, Eric T Wittbrodt, Seoyoung C Kim
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety. OBJECTIVE: Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed. METHODS: A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28315192/discrete-choice-experiment-attribute-selection-using-a-multinational-interview-study-treatment-features-important-to-patients-with-type-2-diabetes-mellitus
#7
Anna Rydén, Stephanie Chen, Emuella Flood, Beverly Romero, Susan Grandy
INTRODUCTION: Methods for discrete choice experiment (DCE) attribute and attribute-level selection have not yet been firmly established and are rarely reported in detail. This paper describes a qualitative study designed to inform the development of a DCE survey designed to examine preferences for glucagon-like peptide-1 receptor agonist (GLP-1RA) treatments among patients with type 2 diabetes mellitus. METHODS: The study involved a literature review, interviews with clinical experts, and interviews with GLP-1RA-experienced (i...
August 2017: Patient
https://www.readbyqxmd.com/read/28058769/upper-and-or-lower-gastrointestinal-adverse-events-with-glucagon-like-peptide-1-receptor-agonists-incidence-and-consequences
#8
Michael Horowitz, Vanita R Aroda, Jenny Han, Elise Hardy, Chris K Rayner
AIMS: To characterize gastrointestinal adverse events (AEs) with different glucagon-like peptide-1 receptor agonists (GLP-1RAs). METHODS: Two retrospective intention-to-treat analyses of 6-month patient-level data were conducted. Data from three studies comparing exenatide once weekly (n = 617) with exenatide twice daily (n = 606) were pooled, and one (DURATION-6) comparing exenatide once weekly (n = 461) with liraglutide (n = 450) was analysed separately...
May 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27899001/drug-interventions-for-the-treatment-of-obesity-in-children-and-adolescents
#9
REVIEW
Emma Mead, Greg Atkinson, Bernd Richter, Maria-Inti Metzendorf, Louise Baur, Nicholas Finer, Eva Corpeleijn, Claire O'Malley, Louisa J Ells
BACKGROUND: Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. OBJECTIVES: To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016...
November 29, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27896683/population-pharmacokinetics-of-an-extended-release-formulation-of-exenatide-following-single-and-multiple-dose-administration
#10
Brenda Cirincione, Jeffrey Edwards, Donald E Mager
Exenatide is a glucagon-like peptide-1 receptor agonist with both immediate- and extended-release (ER) formulations that are approved for the treatment of type 2 diabetes mellitus. Long-term exposure from the ER formulation is achieved through slow peptide release from a degradable microsphere formulation. The goal of this analysis was to develop a pharmacokinetic model for the ER formulation following single and once-weekly multiple-dose administration. Pharmacokinetic data were collected from two clinical trials-one that evaluated single-dose administration of 2...
March 2017: AAPS Journal
https://www.readbyqxmd.com/read/27559996/effects-of-pluronic-f127-peg-multi-gel-core-on-the-release-profile-and-pharmacodynamics-of-exenatide-loaded-in-plga-microspheres
#11
Puxiu Wang, Qian Wang, Tianyang Ren, Haoyu Gong, Jingxin Gou, Yu Zhang, Cuifang Cai, Xing Tang
Pluronic F127 and PEG as a multi-gel-core were used to prepare Exenatide-loaded microspheres and store the drug within the microspheres. Also, the sol-gel transition and novel functions of the Pluronic F127-PEG gel core were investigated.Microspheres with a multi-gel-core (GCMs) and without a multi-gel-core (Ms) were compared in terms of the rate of PLGA degradation, therelease kinetics in vitro and the efficacy in KKAy mice. The drug release of GCMs was at a constant rate, and slower than Ms. In addition, after the KKAy mice were given Exenatide for 55days, the blood glucose concentration and HbA1c concentration in the GCMs group were lower than that in the Ms group...
November 1, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27398720/exenatide-treatment-alone-improves-%C3%AE-cell-function-in-a-canine-model-of-pre-diabetes
#12
Viorica Ionut, Orison O Woolcott, Hasmik J Mkrtchyan, Darko Stefanovski, Morvarid Kabir, Malini S Iyer, Huiwen Liu, Ana V B Castro, Qiang Wu, Josiane L Broussard, Cathryn M Kolka, Isaac Asare-Bediako, Richard N Bergman
BACKGROUND: Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes. OBJECTIVE: We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines. DESIGN AND METHODS: After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg). After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7) or placebo (n = 7) for 12 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27037787/adverse-effects-of-incretin-based-therapies-on-major-cardiovascular-and-arrhythmia-events-meta-analysis-of-randomized-trials
#13
Tiansheng Wang, Fei Wang, Junwen Zhou, Huilin Tang, Sharon Giovenale
BACKGROUND: Recent cardiovascular outcome trials of incretin based therapies (IBT) in type 2 diabetes have not demonstrated either benefit or harm in terms of major adverse cardiovascular events (MACE). Earlier meta-analyses showed conflicting results but were limited in methodology. We aimed to perform an updated meta-analysis of all available incretin therapies on the incidence of MACE plus arrhythmia and heart failure. METHODS: We identified studies published through November 2014 by searching electronic databases and reference lists...
April 2, 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/27009108/comparison-of-exenatide-with-biphasic-insulin-aspart-30-on-glucose-variability-in-type-2-diabetes-study-protocol-for-a-randomized-controlled-trial
#14
RANDOMIZED CONTROLLED TRIAL
Shaoyong Xu, Xiangyang Liu, Jie Ming, Qiuhe Ji
BACKGROUND: Apart from the mean level of glycemic control, the extent of glucose excursions is another important issue to consider in type 2 diabetes mellitus (T2DM) management. Studies have showed that fluctuations of glucose seem to have more deleterious effects than sustained hyperglycemia in the development of diabetic complications as acute glucose swings activate the oxidative stress. However, until now, no randomized controlled trials have been conducted with the primary aim to evaluate glycemic fluctuation in the comparison between twice-daily exenatide and other treatment paradigms (for example, biphasic insulin aspart 30)...
March 24, 2016: Trials
https://www.readbyqxmd.com/read/26930186/hydrogel-drug-delivery-system-using-self-cleaving-covalent-linkers-for-once-a-week-administration-of-exenatide
#15
Eric L Schneider, Jeff Henise, Ralph Reid, Gary W Ashley, Daniel V Santi
We have developed a unique long-acting drug-delivery system for the GLP-1 agonist exenatide. The peptide was covalently attached to Tetra-PEG hydrogel microspheres by a cleavable β-eliminative linker; upon s.c. injection, the exenatide is slowly released at a rate dictated by the linker. A second β-eliminative linker with a slower cleavage rate was incorporated in polymer cross-links to trigger gel degradation after drug release. The uniform 40 μm microspheres were fabricated using a flow-focusing microfluidic device and in situ polymerization within droplets...
May 18, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/26924394/glp-1-receptor-agonist-promotes-brown-remodelling-in-mouse-white-adipose-tissue-through-sirt1
#16
Fen Xu, Beisi Lin, Xiaobin Zheng, Zonglan Chen, Huanyi Cao, Haixia Xu, Hua Liang, Jianping Weng
AIMS/HYPOTHESIS: Accumulating evidence has revealed the significant role of glucagon-like peptide-1 (GLP-1) in weight loss. Sirtuin 1 (SIRT1) plays a vital role in the regulation of lipid metabolism. Here, we investigated the contribution of lipolytic and oxidative changes in white adipose tissue (WAT) to the weight-lowering effect induced by the GLP-1 receptor (GLP-1R) agonist exenatide (exendin-4) in mice. We also looked at the role of SIRT1 in this process. METHODS: C57BL/6J mice and Sirt1 (+/-) mice were treated with exenatide (24 nmol/kg) or an NaCl solution (154 mmol/l) control i...
May 2016: Diabetologia
https://www.readbyqxmd.com/read/26857900/long-acting-phospholipid-gel-of-exenatide-for-long-term-therapy-of-type-ii-diabetes
#17
Mei Hu, Yu Zhang, Nanxi Xiang, Ying Zhong, Tao Gong, Zhi-Rong Zhang, Yao Fu
PURPOSE: This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. METHODS: In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXT phospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution...
2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/26691396/patient-reported-outcome-results-in-patients-with-type-2-diabetes-treated-with-once-weekly-dulaglutide-data-from-the-award-phase-iii-clinical-trial-programme
#18
RANDOMIZED CONTROLLED TRIAL
M Yu, K Van Brunt, O J Varnado, K S Boye
We evaluated patient-reported outcome (PRO) measures from the Assessment of Weekly AdministRation of LY2189265 (dulaglutide) in Diabetes (AWARD) clinical trial programme for dulaglutide (1.5 mg and 0.75 mg) in patients with type 2 diabetes (T2D). The Impact of Weight on Self-Perception (IW-SP), Impact of Weight on Ability to Perform Physical Activities of Daily Living (APPADL), Impact of Weight on Quality of Life-Lite, EQ-5D, Diabetes Treatment Satisfaction Questionnaire (DTSQ), Diabetes Symptom Checklist-Revised and Adult Low Blood Sugar Survey were administered and analysed for changes from baseline in one or more AWARD studies...
April 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/26511102/review-of-head-to-head-comparisons-of-glucagon-like-peptide-1-receptor-agonists
#19
REVIEW
Sten Madsbad
Currently, six glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for treating type 2 diabetes. These fall into two classes based on their receptor activation: short-acting exenatide twice daily and lixisenatide once daily; and longer-acting liraglutide once daily, exenatide once weekly, albiglutide once weekly and dulaglutide once weekly. The phase III trial of a seventh GLP-1RA, taspoglutide once weekly, was stopped because of unacceptable adverse events (AEs). Nine phase III head-to-head trials and one large phase II study have compared the efficacy and safety of these seven GLP-1RAs...
April 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/26242767/insulin-degludec-liraglutide-a-review-in-type-2-diabetes
#20
REVIEW
Sarah L Greig, Lesley J Scott
Insulin degludec/liraglutide (Xultophy(®)), a fixed-ratio combination of an ultra-long-acting insulin analogue and a glucagon-like protein-1 (GLP-1) receptor agonist, is available in the EU for the management of inadequately controlled type 2 diabetes. Once-daily subcutaneous insulin degludec/liraglutide as add-on therapy to oral antidiabetics was effective and generally well tolerated in adults with inadequately controlled type 2 diabetes in several well designed 26-week phase III trials. In insulin-naive patients, add-on insulin degludec/liraglutide provided significantly greater improvements in glycated haemoglobin (HbA1c) levels than add-on insulin degludec, liraglutide or placebo, or unchanged GLP-1 receptor agonists (i...
September 2015: Drugs
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