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Sebastian Wiberg, Jesper Kjaergaard, Henrik Schmidt, Jakob Hartvig Thomsen, Martin Frydland, Matilde Winther-Jensen, Matias Greve Lindholm, Dan Eik Høfsten, Thomas Engstrøm, Lars Køber, Jacob Eifer Møller, Christian Hassager
OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm...
February 2018: Critical Care Medicine
Bhargav Prasad Kodaganti, Pavithra Mukunda, Pravinkumar Dakshinamurthy, Yogendra Manjunath, Bharath Ravindra Shenoy, Veeresha Kamanagowda, Bairavabalakumar Natarajan, Amol Maliwalave, Divya Unnikrishnan, Sathyabalan Murugesan, Vivek Halan, Maloy Ghosh, Sunit Maity
Exendin-4 is a GLP 1 agonist incretin-mimetic peptide hormone comprising 39 amino acids. Exenatide (Byetta(®)) is a chemically synthesized version of Exendin-4 with an additional C-terminal amidation. Exenatide acts as a GLP-1 receptor agonist. This paper illustrates the method adopted for cloning, fermentation and purification of recombinant Exendin-4 analog expressed in Escherichia coli. The biologically expressed analog was extensively characterized using different orthogonal methods to confirm their biological activity and physicochemical properties...
July 2017: Biologicals: Journal of the International Association of Biological Standardization
Qing Qiao, Kristina Johnsson, Susan Grandy, Karel Kostev
BACKGROUND: The aim was to investigate real-world treatment outcomes and tolerability of GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes in Germany. METHODS: Patients from 323 primary care practices who started any GLP-1RA therapy (89 Byetta, 108 Bydureon, 347 Victoza patients) between January 1, 2011, and December 31, 2013 (index date) were analyzed retrospectively (Disease Analyzer database, Germany). Changes from baseline in HbA1c, weight, and hypoglycemia were evaluated in 3 follow-up periods of 0-6, 7-12, and 13-18 months...
March 2017: Journal of Diabetes Science and Technology
P Salehi, I Hsu, C G Azen, S D Mittelman, M E Geffner, D Jeandron
BACKGROUND: Prader-Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin-4]; AstraZeneca, Wilmington DE) is a GLP-1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS. OBJECTIVE: The objective of this study is to determine the effect of a 6-month trial of exenatide on appetite, weight and gut hormones in youth with PWS...
June 2017: Pediatric Obesity
Christian Hölscher
Type 2 diabetes has been identified as a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). In the brains of patients with AD and PD, insulin signaling is impaired. This finding has motivated new research that showed good effects using drugs that initially had been developed to treat diabetes. Preclinical studies showed good neuroprotective effects applying insulin or long lasting analogues of incretin peptides. In transgenic animal models of AD or PD, analogues of the incretin GLP-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality and reduced the symptoms of the diseases...
October 25, 2014: Sheng Li Xue Bao: [Acta Physiologica Sinica]
A J Scheen
Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes. The microsphere technology permits a prolonged absorption of exenatide from the subcutaneous depot, which allows one injection per week instead of two injections per day with the initial formulation of exenatide (Byetta). The clinical development programme DURATION showed that exenatide 2 mg once weekly more markedly reduces glycated haemoglobin (HbA(1c)), with a similar weight loss but a better digestive tolerance profile (less nausea and vomiting after treatment initiation), compared with the twice daily 10 microg exenatide...
April 2014: Revue Médicale de Liège
Udo Stauder, Diplom Enginee, Hina Elton, Alfred Penfornis, Steve Edelman
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are a relatively recent addition to the treatment options for type 2 diabetes mellitus (T2DM) and are administered using prefilled pen devices. METHOD: In this open-label task and interview-based pilot study, 3 GLP-1 receptor agonist pen devices-exenatide (Byetta(®), Bristol-Myers Squibb/AstraZeneca), liraglutide (Victoza(®), Novo Nordisk), and lixisenatide (Lyxumia(®), Sanofi-Aventis)-were comparatively assessed in a randomized order in 30 participants with T2DM for ease of use, using a series of key performance measures (time taken to complete a series of tasks, number of user errors [successful performance], and user satisfaction rating)...
January 2014: Journal of Diabetes Science and Technology
E I Shakhmatova, E V Pimenova, Zh V Shchutskaia
The renal osmoregulatory function was studied in patients with type 2 diabetes mellitus (DM). The renal response to water loading (0.7% b.w.) and simultaneous exenatide (byetta) injection (5 microg) exhibited variation and was dependent on the degree of hyperglycemia. Effective solute-free water excretion was observed in patients with well-controlled DM (HbAlc 6.0 +/- 0.1%), in which CH20 changed from -0.67 +/- 0.2 mL/min to 0.72 +/- 0.2 mL/min. This reaction was absent in patients with poorly controlled DM (HbAlc 8...
2014: Eksperimental'naia i Klinicheskaia Farmakologiia
Konrad Talbot
The prevalence of Alzheimer's disease is increasing rapidly in the absence of truly effective therapies. A promising strategy for developing such therapies is the treatment of brain insulin resistance, a common and early feature of Alzheimer's disease, closely tied to cognitive decline and capable of promoting many biological abnormalities in the disorder. The proximal cause of brain insulin resistance appears to be neuronal elevation in the serine phosphorylation of IRS-1, most likely due to amyloid-β-triggered microglial release of proinflammatory cytokines...
2014: Neurodegenerative Disease Management
Nassima Amarouche, Matthieu Giraud, Luciano Forni, Alessandro Butte, F Edwards, Nicolas Borie, Jean-Hugues Renault
Protected synthetic peptide intermediates are often hydrophobic and not soluble in most common solvents. They are thus difficult to purify by preparative reversed-phase high-performance liquid chromatography (RP-HPLC), usually used for industrial production. It is then challenging to develop alternative chromatographic purification processes. Support-free liquid-liquid chromatographic techniques, including both hydrostatic (centrifugal partition chromatography or CPC) and hydrodynamic (counter-current chromatography or CCC) devices, are mainly involved in phytochemical studies but have also been applied to synthetic peptide purification...
April 11, 2014: Journal of Chromatography. A
Paul L McCormack
Exenatide, administered subcutaneously twice daily (Byetta(®)), is a synthetic version of the natural peptide exendin-4, which is a glucagon-like peptide-1 (GLP-1) receptor agonist (incretin mimetic). Exenatide binds to the GLP-1 receptor with the same affinity as GLP-1, but has a much longer half-life, since it is not degraded by the enzyme dipeptidyl peptidase-4. Exenatide twice daily enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, slows gastric emptying and reduces caloric intake...
March 2014: Drugs
Yunpeng Cai, Liangming Wei, Liuqing Ma, Xiwen Huang, Anqi Tao, Zhenguo Liu, Weien Yuan
Exenatide has been widely used for the treatment of type 2 diabetes mellitus. However, its short plasma half-life of 2.4 hours has limited its clinical application. The exenatide products on the market, twice-daily Byetta™ and once-weekly Bydureon™ (both Amylin Pharmaceuticals, San Diego, CA, USA), are still not perfect. Many researchers have attempted to prolong the acting time of exenatide by preparing sustained-release dosage forms, modifying its structure, gene therapies, and other means. This review summarizes recent advances in long-acting exenatide preparations...
2013: Drug Design, Development and Therapy
Stuart A Ross, Jane Ballantine
OBJECTIVE: To evaluate the efficacy and safety of the available glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exenatide and liraglutide (marketed as Byetta * and Victoza † , respectively) in first- or second-line pharmacotherapy for type 2 diabetes (T2D), described here as 'early use'. RESEARCH DESIGN AND METHODS: MEDLINE, EMBASE and Google Scholar databases were queried for clinical trial reports using the terms incretin, GLP-1, exenatide and liraglutide...
December 2013: Current Medical Research and Opinion
Christina M Buchanan, Zhenzhen Peng, Aiko Cefre, Vijayalekshmi Sarojini
Peptide hormones that modulate insulin secretion have been recognized to have therapeutic potential, with peptides such as amylin (pramlintide acetate, Symlin) and exendin-4 (exenatide, Byetta) now commercially available. Preptin is a peptide that has been shown to increase insulin secretion in vitro and in vivo. Here, we describe the first chemical synthesis and analysis of a short series of preptin analogues based on the rat preptin sequence. Phe 21 in the preptin sequence was substituted with the non-protein amino acids D-Phe, D-Hphe, 3-aminobenzoic acid and 1-aminocyclooctane-1-carboxylic acid, which rendered the preptin analogues resistant to chymotryptic protease hydrolysis at this position...
October 2013: Chemical Biology & Drug Design
J Perusicová, I Haladová, P Pit'hová, D Acsová, J Belobrádková, A Belzová, K Berková, B Dolezalová, H Dvoráková, K Hejnicová, M Hudcová, D Kallmünzerová, Z Krejsová, G Markofová, H Müllerová, K Owen, M Pelikánová, L Raclavská, E Racická, O Skarpová, A Váchová, A Veselá, J Vyoralos, J Broz, T Edelsberger, M Honka, T Hrdina, P Chmura, J Tosovský
UNLABELLED: BIBY STUDY OBJECTIVE: To obtain experience with exenatide treatment (Byetta) in patients with diabetes mellitus type 2 in a common clinical practice ofdiabetology departments. TYPE OF OBSERVATION: Observational study conducted by a randomly selected group of outpatient medical practitioners from 28 diabetology departments in the Czech Republic. OBSERVED AND ASSESSED POPULATION: 465 patients underwent at least three months of Byetta treatment; 347 persons (74.6% ofthe research population) stayed forthe extended observation of 6-12 months...
March 2013: Vnitr̆ní Lékar̆ství
J Perušičová, P Piťhová, I Haladová, A Pracovní Skupina Diabetologů, D Acsová, J Bělobrádková, A Belzová, K Berková, B Doležalová, H Dvořáková, K Hejnicová, M Hudcová, D Kallmünzerová, Z Krejsová, G Markofová, H Müllerová, K Owen, M Pelikánová, L Raclavská, E Račická, O Skarpová, A Váchová, A Veselá, J Vyoralová, J Brož, T Edelsberger, M Honka, T Hrdina, P Chmura, J Tosovsky
UNLABELLED: BIBYII STUDY OBJECTIVE: To obtain experience with longterm (24 months) exenatide treatment (Byetta) in patients with diabetes mellitus type 2 from a common clinical practice of diabetology departments in the Czech Republic. TYPE OF OBSERVATION: Observational study conducted by a randomly selected group of outpatient medical practitioners from 28 diabetology departments in the Czech Republic. OBSERVED AND ASSESSED POPULATION: From the original population of 465 patients, who underwent a minimum of three months Byetta treatment, 169 patients (36...
April 2013: Vnitr̆ní Lékar̆ství
Lavakumar Reddy Aramadhaka, Alyson Prorock, Bojan Dragulev, Yongde Bao, Jay W Fox
Like most natural product libraries animal venoms have long been recognized as potentially rich source of biologically active molecules with the potential to be mined for the discovery of drugs, drug leads and/or biosimilars. In this work we demonstrate as a proof of concept a novel approach to explore venoms for potential biosimilarity to other drugs based on their ability to alter the transcriptomes of test cell lines followed by informatic searches and Connectivity Mapping to match the action of the venom on the cell gene expression to that of other drugs in the Connectivity Map (C-Map) database...
July 2013: Toxicon: Official Journal of the International Society on Toxinology
E I Shakhmatova, Zh V Shutskaia, M E Vladimirova, A I Gorelov, A I Gorbunov, Iu V Natochin
Exenatide effect was studied in 55 human including 38 patients with type 2 diabetes mellitus without signs of diabetic nephropathy and primary renal diseases. Preliminary study with water load in volume from 0.5 to 1% b.w. showed that water load equal to 0.7% b.w. caused significant increase in urine excretion. The rise of diuresis after 10 microg Byetta (exenatide) injection and simultaneous water load of 0.7% of b.w. depended on increase in solute-free water clearance. Thus, exenatide (mimetic of GLP-1) action let us to consider its possible role as component of osmoregulation system in human...
August 2012: Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova
Kwang-Chul Kwon, Ramya Nityanandam, James S New, Henry Daniell
Glucagon-like peptide (GLP-1) increases insulin secretion but is rapidly degraded (half-life: 2 min in circulation). GLP-1 analogue, exenatide (Byetta) has a longer half-life (3.3-4 h) with potent insulinotropic effects but requires cold storage, daily abdominal injections with short shelf life. Because patients with diabetes take >60 000 injections in their life time, alternative delivery methods are highly desired. Exenatide is ideal for oral delivery because insulinotropism is glucose dependent, with reduced risk of hypoglycaemia even at higher doses...
January 2013: Plant Biotechnology Journal
Christian Hölscher
The current understanding of neurodegenerative processes in sporadic diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) or multiple sclerosis is very limited. Several risk factors have been identified that may shed light on the underlying mechanisms that initiate the neurodegeneration. Type 2 diabetes mellitus has been identified as a risk factor for AD and PD. In AD patients, desensitization of insulin receptors in the brain has been shown, even in non-diabetic patients. Insulin acts as a growth factor in the brain and supports neuronal repair, dendritic sprouting and synaptogenesis, and protection from oxidative stress...
October 1, 2012: CNS Drugs
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