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https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#1
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28781108/exenatide-once-weekly-versus-placebo-in-parkinson-s-disease-a-randomised-double-blind-placebo-controlled-trial
#2
Dilan Athauda, Kate Maclagan, Simon S Skene, Martha Bajwa-Joseph, Dawn Letchford, Kashfia Chowdhury, Steve Hibbert, Natalia Budnik, Luca Zampedri, John Dickson, Yazhou Li, Iciar Aviles-Olmos, Thomas T Warner, Patricia Limousin, Andrew J Lees, Nigel H Greig, Susan Tebbs, Thomas Foltynie
BACKGROUND: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period...
August 3, 2017: Lancet
https://www.readbyqxmd.com/read/28777758/is-exenatide-a-treatment-for-parkinson-s-disease
#3
Dilan Athauda, Richard Wyse, Patrik Brundin, Thomas Foltynie
There is growing interest in the use of glucagon-like peptide-1 agonists as treatments for Parkinson's disease following the recent publication of the results of the Exenatide-PD trial. In this randomized, double-blind, placebo controlled trial, patients with moderate stage Parkinson's disease treated with once-weekly subcutaneous injections of exenatide 2 mg (Bydureon) for 48 weeks, had a 3.5-point advantage over the placebo group in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (Part 3) in the practically defined OFF medication state, 12 weeks after cessation of the trial drug...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28755389/no-calcitonin-change-in-a-person-taking-dulaglutide-diagnosed-with-pre-existing-medullary-thyroid-cancer
#4
S I Sherman, R T Kloos, R M Tuttle, A Pontecorvi, H Völzke, K Harper, C Vance, J T Alston, A L Usborne, K W Sloop, M Lakshmanan
BACKGROUND: Glucagon-like peptide-1 receptor agonists, such as dulaglutide, exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus. Although these drugs provide substantial glycaemic control, studies in rodents have prompted concerns about the development of medullary thyroid carcinoma. These data are reflected in the US package insert, with boxed warnings and product labelling noting the occurrence of these tumours after clinically relevant exposures in rodents, and contraindicating glucagon-like peptide-1 receptor agonist use in people with a personal or family history of medullary thyroid carcinoma or in people with multiple endocrine neoplasia type 2...
July 29, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28748377/microvascular-effects-of-glucagon-like-peptide-1-receptor-agonists-in-type-2-diabetes-a-meta-analysis-of-randomized-controlled-trials
#5
Ilaria Dicembrini, Besmir Nreu, Alessia Scatena, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci, Matteo Monami
AIMS: Results with GLP1-receptor agonists (GLP-1RA) on microvascular complications of diabetes are contrasting. In trials designed for cardiovascular outcomes, both liraglutide and semaglutide were associated with a relevant reduction in the incidence and progression of nephropathy. On the other hand, in the same trials, semaglutide was associated with an increased progression of retinopathy, and a similar trend was observed for liraglutide. This meta-analysis is aimed at assessing the effects of GLP-1RA on retinopathy and nephropathy...
July 27, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28734203/exenatide-mitigated-diet-induced-vascular-aging-and-atherosclerotic-plaque-growth-in-apoe-deficient-mice-under-chronic-stress
#6
Guang Yang, Yanna Lei, Aiko Inoue, Limei Piao, Lina Hu, Haiying Jiang, Takeshi Sasaki, Hongxian Wu, Wenhu Xu, Chenglin Yu, Guangxian Zhao, Shinyu Ogasawara, Kenji Okumura, Masafumi Kuzuya, Xian-Wu Cheng
BACKGROUND AND AIMS: Exposure to psychosocial stress is a risk factor for cardiovascular disorders. Because the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist prevents cardiovascular injury, we investigated the beneficial effects and mechanism of the GLP-1 analogue exenatide on stress-related vascular senescence and atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat (HF) diet. METHODS: ApoE(-/-) mice fed the HF diet were assigned to non-stressed and immobilized-stress groups for 12 weeks...
July 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28730824/glucagon-like-peptide-1-analogues-exenatide-and-liraglutide-exert-inhibitory-effect-on-the-early-phase-of-liver-regeneration-after-partial-hepatectomy-in-rats
#7
J Fontana, O Kučera, V Mezera, M Anděl, Z Červinková
Glucagon-like peptide-1 (GLP-1) is an incretin known for proliferative and antiapoptotic effects on various tissues. Exenatide and Liraglutide are GLP-1 analogues used in clinical practice as antidiabetic drugs. Since GLP-1 and its analogues exert significant effect on liver metabolism and since changes in intermediary metabolism play an important role in the process of liver regeneration, we decided to determine the effect of Exenatide and Liraglutide on the early phase of liver regeneration and selected metabolic parameters in a model of 2/3 partial hepatectomy (PHx) in rats...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28724607/renal-hemodynamic-effects-of-glucagon-like-peptide-1-agonist-are-mediated-by-nitric-oxide-but-not-prostaglandin
#8
Scott Culver Thomson, Ali Kashkouli, Zhi Zhao Liu, Prabhleen Singh
The incretin hormone, glucagon like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv)...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28721043/preparation-of-exenatide-loaded-linear-poly-ethylene-glycol-brush-poly-l-lysine-block-copolymer-potential-implications-on-diabetic-nephropathy
#9
Fei Tong
The poly(ethylene glycol)-b-brush poly(l-lysine) polymer (PEG-b-(PELG50-g-PLL3)) was synthesized and evaluated as a nanocarrier for prolonging delivery of exenatide through the abdominal subcutaneous injection route. The isoelectric point of exenatide was 4.86, and exenatide could combine with PEG-b-(PELG50-g-PLL3) polymers via electrostatic interactions at pH 7.4. This polymer was a good candidate for achieving prolonged drug delivery for exenatide, considering its high molecular weight. Besides the physicochemical characterization of the polymer, in vitro and in vivo applications were researched as a sustained exenatide delivery system...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28700374/exenatide-induced-panniculitis-utility-of-the-acid-fast-stain-to-identify-injected-microspheres
#10
Vidal I Claudia, Chaudhry Sofia, Burkemper M Nicole
No abstract text is available yet for this article.
July 7, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28698254/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-the-glucagon-like-peptide-1-receptor-agonist-exenatide-to-characterize-its-antiobesity-effects-in-diet-induced-obese-mice
#11
Shinji Iwasaki, Teruki Hamada, Ikumi Chisaki, Tomohiro Andou, Noriyasu Sano, Atsutoshi Furuta, Nobuyuki Amano
In addition to their potent antidiabetic effects, glucagon-like peptide-1 (GLP-1) analogs lower body weight in humans. Hence, agonistic targeting of the GLP-1 receptor could be a valid approach to target obesity. However, quantitative analyses of the pharmacokinetic/pharmacodynamic (PK/PD) relationship between GLP-1 analogs and their antiobesity effect have not been reported in either animals or humans. Therefore, the present study was performed to establish a mechanism-based PK/PD model of GLP-1 receptor agonists using the GLP-1 analog exenatide for the development of promising new antiobesity drugs...
September 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28685973/efficacy-and-tolerability-of-the-new-autoinjected-suspension-of-exenatide-once-weekly-versus-exenatide-twice-daily-in-patients-with-type-2-diabetes
#12
Carol H Wysham, Julio Rosenstock, Marion L Vetter, Fang Dong, Peter Öhman, Nayyar Iqbal
AIMS: To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol® diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS: This randomized, open-label, controlled study in patients with type 2 diabetes on diet and exercise or stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10 μg) for 28 weeks...
July 7, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28679129/combined-treatment-with-exenatide-and-cyclosporine-a-or-parstatin-1-26-results-in-enhanced-reduction-of-infarct-size-in-a-rabbit-model
#13
Panagiotis Alexopoulos, Konstantina Panoutsopoulou, George Vogiatzis, Efstratios Koletsis, Dimitrios Dougenis, Nikos E Tsopanoglou
Exenatide and cyclosporine A have been shown to moderately protect against myocardial reperfusion injury leading to reduction of infarct size in patients. Our objective was to investigate whether the combined treatment with exenatide (glucagon-like peptide 1 receptor agonist) and cyclosporine A or parstatin 1-26 (inhibitors of mitochondrial permeability transition pore and/or inflammation) is more beneficial than either agent alone. Rabbits underwent 40 minutes of ischemia and 120 minutes of reperfusion. Intravenous bolus administration of exenatide or cyclosporine A, 10 minutes before reperfusion, reduced infarct size by 38% (P < 0...
July 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28674957/a-review-of-the-long-term-efficacy-tolerability-and-safety-of-exenatide-once-weekly-for-type-2-diabetes
#14
REVIEW
Stefano Genovese, Edoardo Mannucci, Antonio Ceriello
INTRODUCTION: Exenatide once weekly (ExeOW, Bydureon(®), Astra Zeneca), a drug belonging to the class of glucagon-like peptide-1 (GLP-1) receptor agonists, is the first agent approved for treatment of type 2 diabetes (T2D) that can be administered on a weekly basis. METHODS: Data concerning treatment of T2D with ExeOW are reviewed with special reference to its long-term efficacy, tolerability, and safety. Relevant literature was identified through the PubMed database from inception to January 2015...
July 3, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28669463/three-year-efficacy-and-safety-of-exenatide-once-weekly-a-pooled-analysis-of-three-trials
#15
Michael E Trautmann, Luc Van Gaal, Jenny Han, Elise Hardy
AIMS: To evaluate the 3-year efficacy and safety of exenatide once weekly (QW) for type 2 diabetes (T2D) in a large clinical population. METHODS: This post hoc analysis of three DURATION studies examined pooled efficacy and adverse events with exenatide QW from the 2.5- to 3-year completer populations; insulin glargine (glargine) was a reference (DURATION-3). Patients randomized to exenatide QW during the controlled study periods continued controlled treatment (DURATION-3) or single-arm treatment (DURATION-1; DURATION-2) with exenatide QW for the study duration...
June 20, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28657399/combination-sglt2-inhibitor-and-glp-1-receptor-agonist-therapy-a-complementary-approach-to-the-treatment-of-type-2-diabetes
#16
Robert S Busch, Michael P Kane
Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia...
June 28, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28640441/adipose-tissue-derived-omentin-1-function-and-regulation
#17
Takuya Watanabe, Kaho Watanabe-Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe
Omentin-1, also known as intelectin-1, is a recently identified novel adipocytokine of 313 amino acids, which is expressed in visceral (omental and epicardial) fat as well as mesothelial cells, vascular cells, airway goblet cells, small intestine, colon, ovary, and plasma. The level of omentin-1 expression in (pre)adipocytes is decreased by glucose/insulin and stimulated by fibroblast growth factor-21 and dexamethasone. Several lines of experimental evidence have shown that omentin-1 plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects via AMP-activated protein kinase/Akt/nuclear factor-κB/mitogen-activated protein kinase (ERK, JNK, and p38) signaling...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28615237/erratum-combination-therapy-with-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-patients-with-poorly-controlled-type-2-diabetes-on-sulfonylurea-plus-metformin-the-qatar-study-diabetes-care-2017-40-325-331
#18
Muhammad Abdul-Ghani, Osama Migahid, Ayman Megahed, John Adams, Curtis Triplitt, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
No abstract text is available yet for this article.
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28612554/-the-preliminary-investigation-of-glp-1-receptor-agonist-on-liver-steatosis-in-obese-mice
#19
Xia Wang, He He, Li-Bo Liang, Mei Zhang, She-Yu Li, Shuang-Qing Li, Zhen-Mei An, Heng-Jian Huang
OBJECTIVES: To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, on liver function and steatosis in obese mice. METHODS: Male c57BL/6J mice (8 weeks old) were divided into high-fat-diet group (for obesity model construction) and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group [H group, intraperitoneal injection 0.02 μg/ (g·d) , high-fat-diet], low-dose exenatide group [L group, intraperitoneal injection 0...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28605180/a-hydrogel-microsphere-drug-delivery-system-that-supports-once-monthly-administration-of-a-glp-1-receptor-agonist
#20
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
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