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https://www.readbyqxmd.com/read/30019627/treatment-with-exenatide-in-acute-ischemic-stroke-trial-protocol-a-prospective-randomized-open-label-blinded-end-point-study-of-exenatide-vs-standard-care-in-post-stroke-hyperglycemia
#1
Claire Muller, N Wah Cheung, Helen Dewey, Leonid Churilov, Sandy Middleton, Vincent Thijs, Elif I Ekinci, Chris Levi, Richard Lindley, Geoffrey Donnan, Mark Parsons, Christopher Bladin
Rationale Post-stroke hyperglycemia occurs in up to 50% of patients presenting with acute ischemic stroke. It reduces the efficacy of thrombolysis, increases infarct size, and worsens clinical outcomes. Insulin-based therapies have generally not been beneficial in treating post-stroke hyperglycemia as they are difficult to implement, may cause hypoglycaemia, possibly increase mortality and worsen clinical outcomes. Exenatide may be a safer, simpler, and more effective alternative to insulin in acute ischemic stroke...
January 1, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/30015142/effects-of-the-multilayer-structures-on-exenatide-release-and-bioactivity-in-microsphere-thermosensitive-hydrogel-system
#2
Puxiu Wang, Yue Li, Mingyan Jiang
Traditional polypeptide-loaded PLGA microspheres (PM) using emulsion electrospray techniques often exhibit unsteady release and limited bioactivity. To solve these two problems, an Exenatide (EXT)-loaded multilayer system composed ofPM and thermosensitive hydrogel was prepared by the emulsion electrospray technique in this study. Hydrogel mixture were loaded in PLGA microspheres as Depot-hydrogel to prepare Gel/PM. The PM/Gel and Gel/PM/Gel systems were obtained by dispersion of PM and Gel/PM into hydrogel mixture, respectively...
May 1, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/30015124/safety-and-efficacy-assessment-of-a-glp-1-mimetic-insulin-glargine-combination-for-treatment-of-feline-diabetes-mellitus
#3
M A Scuderi, M Ribeiro Petito, S Unniappan, C Waldner, S Mehain, C J McMillian, E C Snead
A commonly used therapeutic strategy for type 2 diabetes mellitus (DM) in humans involves the use of synthetic incretin hormone-based therapies including exenatide, a glucagon-like pepetide-1 hormone agonist. Glucagon-like pepetide-1 agonists can be used alone or as an ancillary therapy with other agents, including insulin and oral antihyperglycemics. Little is known about the role of these therapies for DM in cats. Therefore, the primary objective of this study was to evaluate the safety and efficacy of short-acting exenatide combined with insulin, as compared to placebo and insulin for the treatment of DM in cats...
May 9, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/30012779/does-glucagon-like-peptide-1-glp-1-receptor-agonist-stimulation-reduce-alcohol-intake-in-patients-with-alcohol-dependence-study-protocol-of-a-randomised-double-blinded-placebo-controlled-clinical-trial
#4
Kerstin K Antonsen, Mette K Klausen, Amanda S Brunchmann, Nina le Dous, Mathias E Jensen, Kamilla Woznica Miskowiak, Patrick M Fisher, Gerda K Thomsen, Henrik Rindom, Thomas P Fahmy, Sabine Vollstaedt-Klein, Helene Benveniste, Nora D Volkow, Ulrik Becker, Claus Ekstrøm, Gitte Moos Knudsen, Tina Vilsbøll, Anders Fink-Jensen
INTRODUCTION: Alcohol dependence is a major public health problem. It is underdiagnosed and undertreated. Even when treated, more than 2/3 of patients in abstinence-oriented treatment will relapse within the first year. Thus, there is an urgent need for efficacious medical treatment of alcohol dependence. Glucagon-like peptide-1 (GLP-1) receptor stimulation has proven to reduce alcohol consumption in preclinical experiments. However, the effect of GLP-1 receptor agonists in humans has to our knowledge, not yet been investigated...
July 16, 2018: BMJ Open
https://www.readbyqxmd.com/read/30003931/glp-1-receptor-agonists-stimulate-angptl8-production-through-the-pi3k-akt-pathway-in-a-glp-1-receptor-dependent-manner
#5
Junling Liu, Kun Yang, Wenhua Xiao, Yunyi Le, Shan Lang, Jingjing Zhang, Rui Wei, Jin Yang, Tianpei Hong
The level of serum angiopoietin-like protein 8 (ANGPTL8), a novel hepatokine, is associated with obesity and type 2 diabetes mellitus (T2DM). To investigate whether serum ANGPTL8 level in patients with T2DM was affected by treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, and to determine whether and how GLP-1R agonists regulated ANGPTL8 production in hepatocytes. A multiple-center trial was conducted in China. Among 240 patients with T2DM enrolled in this trial, 195 patients adhered to a 16-week exenatide treatment and follow-up...
July 9, 2018: Peptides
https://www.readbyqxmd.com/read/29985448/simultaneous-glp-1-receptor-activation-and-angiotensin-receptor-blockade-increase-natriuresis-independent-of-altered-arterial-pressure-in-obese-oletf-rats
#6
Ruben Rodriguez, Meagan Moreno, Andrew Y Lee, Jose A Godoy-Lugo, Daisuke Nakano, Akira Nishiyama, David Parkes, Mouhamed S Awayda, Rudy M Ortiz
Obesity is associated with an inappropriately activated renin-angiotensin-aldosterone system, suppressed glucagon-like peptide-1 (GLP-1), increased renal Na+ reabsorption, and hypertension. To assess the link between GLP-1 and angiotensin receptor type 1 (AT1 ) signaling on obesity-associated impairment of urinary Na+ excretion (UNa V) and elevated arterial pressure, we measured mean arterial pressure (MAP) and heart rate by radiotelemetry and metabolic parameters for 40 days. We tested the hypothesis that stimulation of GLP-1 signaling provides added benefit to blockade of AT1 by increasing UNa V and further reducing arterial pressure in the following groups: (1) untreated Long-Evans Tokushima Otsuka (LETO) rats (n = 7); (2) untreated Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 9); (3) OLETF + ARB (ARB; 10 mg olmesartan/kg/day; n = 9); (4) OLETF + GLP-1 receptor agonist (EXE; 10 µg exenatide/kg/day; n = 7); and (5) OLETF + ARB + EXE (Combo; n = 6)...
July 9, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29950475/protocol-for-meal-time-administration-of-exenatide-for-glycaemic-control-in-type-1-diabetes-cases-the-mag1c-trial-a-randomised-double-blinded-placebo-controlled-trial
#7
Nicklas Järvelä Johansen, Thomas Fremming Dejgaard, Asger Lund, Tina Vilsbøll, Henrik Ullits Andersen, Filip Krag Knop
INTRODUCTION: Persons with type 1 diabetes require intensive insulin therapy to achieve glycaemic control, but side effects, including hypoglycaemia and weight gain, may reduce treatment compliance. We hypothesise that add-on treatment of the short-acting glucagon-like peptide-1 receptor agonist, exenatide, to insulin therapy in persons with type 1 diabetes will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia...
June 27, 2018: BMJ Open
https://www.readbyqxmd.com/read/29949126/clinical-pharmacology-of-glucagon-like-peptide-1-receptor-agonists
#8
REVIEW
Dimitrios Sfairopoulos, Stavros Liatis, Stelios Tigas, Evangelos Liberopoulos
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an important asset in the armamentarium for the treatment of type 2 diabetes mellitus (type 2 DM). Incretin failure is a critical etiopathogenetic feature of type 2 DM, which, if reversed, results in improved glycaemic control. GLP-1 RAs are injectable peptides that resemble the structure and function of endogenous incretin GLP-1, but as they are not deactivated by the dipeptidyl peptidase-4 (DPP-4), their half-life is prolonged compared with native GLP-1...
June 12, 2018: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29949016/a-randomized-controlled-trial-of-dapagliflozin-plus-once-weekly-exenatide-versus-placebo-in-individuals-with-obesity-and-without-diabetes-metabolic-effects-and-markers-associated-with-bodyweight-loss
#9
Maria J Pereira, Per Lundkvist, Prasad G Kamble, Joey Lau, Julian G Martins, C David Sjöström, Volker Schnecke, Anna Walentinsson, Eva Johnsson, Jan W Eriksson
INTRODUCTION: The sodium-glucose cotransporter 2 inhibitor dapagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via differing and complementary mechanisms. This post hoc analysis investigated the metabolic effects and baseline associations with bodyweight loss on coadministration of dapagliflozin and exenatide once weekly (QW) among adults with obesity and without diabetes. METHODS: In the primary trial, adults with obesity and without diabetes [n = 50; 18-70 years; body mass index (BMI) 30-45 kg/m2 ] were randomized to double-blind oral dapagliflozin 10 mg (DAPA) once daily plus subcutaneous long-acting exenatide 2 mg QW (ExQW) or placebo over 24 weeks, followed by an open-label extension from 24-52 weeks during which all participants received active treatment...
June 13, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29948981/enhancing-stability-of-exenatide-containing-pressurized-metered-dose-inhaler-via-reverse-microemulsion-system
#10
Xing Li, Ying Huang, Zhengwei Huang, Xiangyu Ma, Ni Dong, Wanxin Chen, Xin Pan, Chuanbin Wu
The dispersibility and stability issues of peptide drugs during preparation and storage hinder the widespread adoption of pressurized metered-dose inhaler (pMDI). This study aimed to develop a reverse microemulsion (RM) of exenatide (EXE) pMDI through a liquid-based bottom-up method, thus to overcome the stability issue of peptide drugs encountered in traditional top-down methods, such as milling down and high-pressure homogenization. In this study, Pluronic® L64 (L64) was chosen as a surfactant to prepare the EXE-RM pMDI formulations with the assistance of ethanol...
June 11, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29932808/shielding-effect-of-a-peg-molecule-of-a-mono-pegylated-peptide-varies-with-peg-chain-length
#11
Ngoc-Thanh Thi Nguyen, Soi Yun, Dong Woo Lim, E K Lee
'Shielding' effect of a conjugated PEG molecule could cause a change in the electrostatic interaction characteristics of a PEGylate. We investigated how PEG chain length (or molecular weight) alters the electrostatic interaction potential of exenatide variants using their mono-PEGylates in a branched and linear form as model PEGylates. First, we performed the experiments to demonstrate the elution time changes of the mono-PEGylates conjugated with various MW PEGs (5, 10, 20, and 40 kD) using cation exchange chromatography (HiTrap® SP) at various pHs (2...
June 22, 2018: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/29932006/semaglutide-the-newest-once-weekly-glp-1-ra-for-type-2-diabetes
#12
Rhianna M Tuchscherer, Angela M Thompson, Jennifer M Trujillo
OBJECTIVE: To review efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide for type 2 diabetes (T2D). DATA SOURCES: A literature search of PubMed/MEDLINE and EMBASE using the term semaglutide was completed through April 2018. A search of clinicaltrials.gov was also conducted. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing the efficacy and/or safety of semaglutide were evaluated...
June 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29924135/exenatide-ameliorates-hepatic-steatosis-and-attenuates-fat-mass-and-fto-gene-expression-through-pi3k-signaling-pathway-in-nonalcoholic-fatty-liver-disease
#13
Shan Li, Xiaoman Wang, Jielei Zhang, Jingyi Li, Xiaogang Liu, Yuanyuan Ma, Chao Han, Lixia Zhang, Lili Zheng
Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29915923/pharmacokinetics-and-clinical-implications-of-semaglutide-a-new-glucagon-like-peptide-glp-1-receptor-agonist
#14
REVIEW
Sylvie Hall, Diana Isaacs, Jennifer N Clements
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) came to market in the year 2005, as a new therapeutic classification, for clinical use in the management of type 2 diabetes mellitus (T2DM). Since 2005, there have been six approved products on the market, with the newest product being semaglutide (Novo Nordisk). Several studies have been conducted and completed evaluating its pharmacokinetics as a once-weekly subcutaneous injection. As a dose of 0.5 or 1 mg, semaglutide has a half-life of 7 days; therefore, it would reach steady state in 4-5 weeks...
June 19, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29915538/efficacy-and-safety-of-once-weekly-semaglutide-for-the-treatment-of-type-2-diabetes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#15
Fang-Hong Shi, Hao Li, Min Cui, Zai-Li Zhang, Zhi-Chun Gu, Xiao-Yan Liu
Background: Semaglutide, a newly once-weekly glucagon like peptide-1 (GLP-1) receptor agonist, has showed a favorable effect on glycaemic control and weight reduction in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to evaluate the clinical efficacy and safety of semaglutide in T2DM. Methods: A comprehensive searching was performed for Phase III randomized controlled trials (RCTs) which reported the efficacy and safety data of semaglutide and other therapies. The efficacy data expressed as weight mean difference (WMD) and the safety data expressed as risk ratios (RRs) were calculated by employing random-effects model...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29912998/safety-of-once-weekly-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes
#16
Juan P Frias
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been found efficacious in the treatment of type 2 diabetes (T2D), demonstrating the ability to lower HbA1c, and having the potential for inducing weight loss and reducing the risk of hypoglycemia, compared with other antihyperglycemic agents. Currently, 4 once-weekly (OW) GLP-1 RAs are approved: albiglutide, dulaglutide, exenatide ER, and recently, semaglutide. This review compares the relative safety of OW GLP-1 RAs, as well as their safety in comparison to other antihyperglycemic agents, using safety data reported in key sponsor-led phase 3 studies of the 4 OW GLP-1 RAs...
June 2018: Journal of Family Practice
https://www.readbyqxmd.com/read/29912997/clinical-efficacy-of-once-weekly-glucagonlike-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes
#17
Timothy S Bailey
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are indicated for restoring normoglycemia in patients with type 2 diabetes (T2D). This review analyzed and compared the efficacy results from 30 trials with the once-weekly (OW) GLP-1 RAs albiglutide, dulaglutide, exenatide extended-release (ER) and semaglutide. The 4 OW GLP-1 RAs showed a higher reduction in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight, when compared to placebo. Semaglutide significantly reduced the HbA1c level (estimated treatment difference [ETD]: -0...
June 2018: Journal of Family Practice
https://www.readbyqxmd.com/read/29907137/expression-of-the-glucagon-like-peptide-1-receptor-and-its-role-in-regulating-autophagy-in-endometrial-cancer
#18
Ranka Kanda, Haruko Hiraike, Osamu Wada-Hiraike, Takayuki Ichinose, Kazunori Nagasaka, Yuko Sasajima, Eiji Ryo, Tomoyuki Fujii, Yutaka Osuga, Takuya Ayabe
BACKGROUND: A previous report showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist (exenatide) induced apoptosis in endometrial cancer cells. However, the pathophysiological role of GLP-1R in endometrial cancer has not been fully elucidated. Here, we investigated the effects of the GLP-1R agonist liraglutide in endometrial cancer cells and examined the association between GLP-1R expression and clinicopathological characteristics in endometrial cancer patients. METHODS: Human Ishikawa endometrial cancer cells were treated with different concentrations of liraglutide...
June 15, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29870275/the-clinical-impact-of-glp-1-receptor-agonists-in-type-2-diabetes-focus-on-the-long-acting-analogs
#19
Helena W Rodbard
GLP-1 receptor agonists (GLP-1 RAs), introduced for clinical use in 2005, have excellent potency in reducing HbA1c and mean glucose, improving fasting plasma glucose, inducing weight loss or protecting against the weight gain associated with insulin therapy, reducing appetite, and delaying gastric emptying. Two of these medications, liraglutide and semaglutide, appear to have cardioprotective effects as reflected in cardiovascular outcomes studies. The GLP-1 RAs are associated with gastrointestinal side effects that tend to diminish over time...
June 2018: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/29862621/achieving-glycaemic-control-without-weight-gain-hypoglycaemia-or-gastrointestinal-adverse-events-in-type-2-diabetes-in-the-sustain-clinical-trial-programme
#20
J Hans DeVries, Cyrus Desouza, Srikanth Bellary, Jeffrey Unger, Oluf K H Hansen, Jeppe Zacho, Vincent Woo
AIM: To evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects. MATERIALS AND METHODS: Data from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug-naïve (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5)...
June 4, 2018: Diabetes, Obesity & Metabolism
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