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Liraglutide

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https://www.readbyqxmd.com/read/28799414/the-clinical-use-of-a-fixed-dose-combination-of-insulin-degludec-and-liraglutide-xultophy-100-3-6-for-the-treatment-of-type-2-diabetes
#1
Kira Harris, Kimberly Lovin Nealy
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the fixed-dose combination of insulin degludec and the glucagon-like peptide-I receptor agonist (GLP-1 RA), liraglutide (IDegLira) in the treatment of type 2 diabetes mellitus (T2DM). DATA SOURCES: A PubMed and MEDLINE search (1966 to July 2017) of the keywords insulin degludec, liraglutide, and type 2 diabetes mellitus was conducted. References were reviewed to identify additional citations...
August 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#2
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/28794087/euglycaemic-ketoacidosis-a-potential-new-hazard-to-plastic-surgery-day-case-and-inpatient-procedures
#3
Aseel Sleiwah, Michael McBride, Claire E Black
A woman aged 44 underwent elective standard abdominoplasty and bilateral mastopexy (superiorly based pedicle with vertical scar) following weight loss of 8.5 stone (53.9 kg) over a 5-year period. She had type 2 diabetes and her antidiabetic medications included metformin, liraglutide and empagliflozin. Towards the end of the first postoperative day, she reported gradual onset of nausea, vomiting and abdominal pain. Her condition continued to deteriorate overnight, becoming tachycardic and tachypnoeic. Urgent investigations showed severe diabetic ketoacidosis with euglycaemia...
August 9, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28793270/pancreatic-islet-blood-flow-dynamics-in-primates
#4
Juan A Diez, Rafael Arrojo E Drigo, Xiaofeng Zheng, Olga V Stelmashenko, Minni Chua, Rayner Rodriguez-Diaz, Masahiro Fukuda, Martin Köhler, Ingo Leibiger, Sai Bo Bo Tun, Yusuf Ali, George J Augustine, Veluchamy A Barathi, Per-Olof Berggren
Blood flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engrafted islets were vascularized and innervated and maintained the cytoarchitecture of in situ islets in the pancreas. Blood flow velocity in the engrafted islets was not affected by increasing blood glucose levels and/or the GLP-1R agonist liraglutide...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28780599/liraglutide-ameliorates-cardiotoxicity-induced-by-doxorubicin-in-rats-through-the-akt-gsk-3%C3%AE-signaling-pathway
#5
Noha A T Abbas, Soad L Kabil
Doxorubicin (Dox)-induced cardiotoxicity constitutes the major adverse effect that limited its use. We investigated the possible protective effects of liraglutide on Dox-induced cardiotoxicity in rats. Rats were divided into the following groups: control group rats received normal saline [1 ml/kg, intraperitoneal (i.p.)]; doxorubicin group rats received doxorubicin (1.25 mg/kg, i.p.), four times per week for 4 weeks; and liraglutide group rats received doxorubicin (1.25 mg/kg, i.p.) four times per week for 4 weeks then received liraglutide (100 μg/kg, i...
August 5, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28771355/peptide-half-life-extension-divalent-small-molecule-albumin-interactions-direct-the-systemic-properties-of-glucagon-like-peptide-1-glp-1-analogues
#6
Esben M Bech, Manuel C Maldonado, Pernille Wismann, Kasper K Sørensen, Søren Blok van Witteloostuijn, Mikkel B Thygesen, Niels Vrang, Jacob Jelsing, Søren L Pedersen, Knud J Jensen
Noncovalent binding of biopharmaceuticals to human serum albumin protects against enzymatic degradation and renal clearance. Herein, we investigated the effect of mono- or divalent small-molecule albumin binders for half-life extension of peptides. For proof-of-principle, the clinically relevant glucagon-like peptide 1 (GLP-1) was functionalized with diflunisal, indomethacin, or both. In vitro, all GLP-1 analogues had subnanomolar GLP-1 receptor potency. Surface plasmon resonance revealed that both small molecules were able to confer albumin affinity to GLP-1 and indicated that affinity is increased for divalent analogues...
August 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28770459/effect-of-liraglutide-on-myocardial-glucose-uptake-and-blood-flow-in-stable-chronic-heart-failure-patients-a-double-blind-randomized-placebo-controlled-live-sub-study
#7
Roni Nielsen, Anders Jorsal, Peter Iversen, Lars Poulsen Tolbod, Kirsten Bouchelouche, Jens Sørensen, Hendrik Johannes Harms, Allan Flyvbjerg, Lise Tarnow, Caroline Kistorp, Ida Gustafsson, Hans Erik Bøtker, Henrik Wiggers
BACKGROUND: The glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR). METHODS AND RESULTS: CHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design...
August 2, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/28768173/the-sustained-effects-of-a-dual-gip-glp-1-receptor-agonist-nnc0090-2746-in-patients-with-type-2-diabetes
#8
Juan Pablo Frias, Edward J Bastyr, Louis Vignati, Matthias H Tschöp, Christophe Schmitt, Klara Owen, Rune Haubo Christensen, Richard D DiMarchi
Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28763870/-effect-of-liraglutide-in-treatment-of-non-alcoholic-fatty-liver-disease-mechanism-of-action-and-research-advances
#9
Y Liu, P P Feng, W Zhu, J P Gong
Non-alcoholic fatty liver disease is a common chronic liver disease closely associated with obesity, hyperlipidemia, and diabetes. It can gradually progress to liver cirrhosis or even hepatocellular carcinoma; however, there are still no specific therapeutic agents for this disease. Liraglutide is a human glucagon-like peptide-1 analogue and has a marked effect in the treatment of type 2 diabetes. At present, many studies indicate that liraglutide also has a certain therapeutic effect on non-alcoholic fatty liver disease during the treatment of type 2 diabetes, but its mechanism of action remains unknown...
June 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28757640/effects-of-peripheral-administration-of-a-neuromedin-u-receptor-2-selective-agonist-on-food-intake-and-body-weight-in-obese-mice
#10
T Kaisho, H Nagai, T Asakawa, N Suzuki, H Fujita, K Matsumiya, N Nishizawa, Y Kanematsu-Yamaki, K Dote, J-I Sakamoto, T Asami, S Takekawa
BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions including regulation of smooth-muscle contraction, blood pressure, stress responses, and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system, respectively. It is reported that the NMU signaling system regulates food intake and body weight via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity...
July 31, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28755389/no-calcitonin-change-in-a-person-taking-dulaglutide-diagnosed-with-pre-existing-medullary-thyroid-cancer
#11
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/28753251/liraglutide-mitigates-tnf-%C3%AE-induced-pro-atherogenic-changes-and-microvesicles-release-in-huvec-from-diabetic-women
#12
Pamela Di Tomo, Paola Lanuti, Natalia Di Pietro, Maria Pompea Antonia Baldassarre, Marco Marchisio, Assunta Pandolfi, Agostino Consoli, Gloria Formoso
BACKGROUND: To evaluate whether exposure to GLP-1 receptor agonist Liraglutide could modulate pro-atherogenic alterations previously observed in endothelial cells obtained by women affected by gestational diabetes, thus exposed in vivo to hyperglycemia, oxidative stress and inflammation and to evaluate endothelial microvesicles (EMV) release, a new reliable biomarker of vascular stress/damage. METHODS: we studied Liraglutide effects and its plausible molecular mechanisms on monocyte cells adhesion and adhesion molecules expression and membrane exposure in control (C-) Human Umbilical Vein Endothelial Cells (HUVEC) as well as in HUVEC of women affected by gestational diabetes (GD) exposed in vitro to TNF-α...
July 28, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28752966/-the-study-of-the-effect-and-mechanism-of-glucagon-like-peptide-1-in-bleomycin-induced-pulmonary-fibrosis-in-mice
#13
Mei Liu, Si Gou, Hai-Tao Chen, Zhong-Hua Chen
OBJECTIVE: To investigate the potential value and mechanisms of glucagon like peptide-1 (GLP-1) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice were treated with a single sublethal dose of BLM (3 mg/kg ) via intratracheal infusion to produce pulmonary fibrosis, and then liraglutide (2 mg/kg) was given to the mice for 28 days by intraperitoneal injection. 28 days after BLM infusion, the number of total cells, macrophages and neutrophils, lymphocytes, and the content of transforming growth factor-beta 1 (TGF-β1) in bronchoalveolar lavage fluid (BALF) were measured...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
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
#14
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/28744119/spatiotemporal-delivery-of-nanoformulated-liraglutide-for-cardiac-regeneration-after-myocardial-infarction
#15
Quan Qi, Lei Lu, Haiqing Li, Zhize Yuan, Gaoxian Chen, Miao Lin, Zhengwen Ruan, Xiaofeng Ye, Zeyu Xiao, Qiang Zhao
The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NP-liraglutide) on experimental MI...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28738426/long-term-effects-of-liraglutide-in-japanese-patients-with-type-2-diabetes-among-the-subgroups-with-different-renal-functions-results-of-2-year-prospective-study
#16
Takeyuki Hiramatsu, Akiko Ozeki, Hideaki Ishikawa, Shinji Furuta
Aims Very few studies have ever examined the effects of long-term (>1 year) administration of liraglutide in patients with type 2 diabetes mellitus (T2DM) and renal impairment. Therefore, we conducted a 2-year study to prospectively examine the effects of liraglutide in those patients. Methods A total of 148 patients with T2DM were enrolled and treated with liraglutide (0.6 or 0.9 mg/day). 97 patients completed the 2-year study without protocol deviations. These patients were divided into 3 groups according to the baseline estimated glomerular filtration ratio (eGFR) (in mL/min/1...
July 24, 2017: Drug Research
https://www.readbyqxmd.com/read/28737448/mast-cell-and-m1-macrophage-infiltration-and-local-pro-inflammatory-factors-were-attenuated-with-incretin-based-therapies-in-obesity-related-glomerulopathy
#17
Jiao He, Geheng Yuan, Fangxiao Cheng, Junqing Zhang, Xiaohui Guo
BACKGROUND: The global increase of obesity parallels the obesity-related glomerulopathy (ORG) epidemic. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists were well recognized to attenuate renal injury independent of glucose control in diabetic nephropathy. There are limited studies focusing on their effects on ORG. We explored the effects of incretin-based therapies on early ORG and the inflammatory responses involved mainly concentrated on mast cell (MC) and macrophage (M) infiltration and local pro-inflammatory factors...
July 24, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28730832/liraglutide-preserves-intracellular-calcium-handling-in-isolated-murine-myocytes-exposed-to-oxidative-stress
#18
S Palee, S C Chattipakorn, N Chattipakorn
In ischemic/reperfusion (I/R) injured hearts, severe oxidative stress occurs and is associated with intracellular calcium (Ca(2+)) overload. Glucagon-Like Peptide 1 (GLP-1) analogues have been shown to exert cardioprotection in I/R heart. However, there is little information regarding the effects of GLP-1 analogue on the intracellular Ca(2+) regulation in the presence of oxidative stress. Therefore, we investigated the effects of GLP-1 analogue, (liraglutide, 10 microM) applied before or after hydrogen peroxide (H(2)O(2), 50 microM) treatment on intracellular Ca(2+) regulation in isolated cardiomyocytes...
July 18, 2017: Physiological Research
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
#19
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/28726152/cardiovascular-outcome-trial-update-in-diabetes-new-evidence-remaining-questions
#20
REVIEW
Rebecca Herbst, Wilburn Bolton, Afreen Shariff, Jennifer B Green
PURPOSE OF REVIEW: Seven trials of new agents to treat type 2 diabetes (T2DM) have been performed to assess cardiovascular (CV) safety. A significant amount of information regarding the effects of drugs in three classes is available, with new data from multiple other trials expected shortly. This article provides a summary of recently completed trials. RECENT FINDINGS: The dipeptidyl peptidase-4 inhibitors studied thus far do not alter the risk of major adverse CV events (MACE)...
September 2017: Current Diabetes Reports
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