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https://www.readbyqxmd.com/read/28726152/cardiovascular-outcome-trial-update-in-diabetes-new-evidence-remaining-questions
#1
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
https://www.readbyqxmd.com/read/28722271/beyond-glycemic-control-a-cross-over-double-blind-24-week-intervention-with-liraglutide-in-type-1-diabetes
#2
M-C Dubé, M D'Amours, S J Weisnagel
AIMS: To investigate the effects of 24 weeks of treatment with liraglutide added to basal/bolus insulin on anthropometric and metabolic parameters in overweight participants with type 1 diabetes. METHODS: In a double-blind cross-over fashion, 15 participants were randomly assigned (1:1) to receive placebo (saline solution) or liraglutide for 24 weeks including a one-month titration period from 0.6 mg to 1.2 mg to 1.8 mg, in addition to their insulin. The treatment was followed by a 1 month wash-out period...
July 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28721686/rationale-for-initiation-and-titration-of-the-basal-insulin-glp-1ra-fixed-ratio-combination-products-ideglira-and-iglarlixi-for-the-management-of-type-2-diabetes
#3
REVIEW
Virginia Valentine, Jennifer Goldman, Jay H Shubrook
Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response...
July 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28717164/glucagon-like-peptide-1-reduces-pancreatic-%C3%AE-cell-mass-through-hypothalamic-neural-pathways-in-high-fat-diet-induced-obese-rats
#4
Hisae Ando, Koro Gotoh, Kansuke Fujiwara, Manabu Anai, Seiichi Chiba, Takayuki Masaki, Tetsuya Kakuma, Hirotaka Shibata
We examined whether glucagon-like peptide-1 (GLP-1) affects β-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713911/glucagon-like-peptide-1-analogue-liraglutide-ameliorates-atherogenesis-via-inhibiting-advanced-glycation-end-product-induced-receptor-for-advanced-glycosylation-end-product-expression-in-apolipoprotein-e-deficient-mice
#5
Peicheng Li, Zhaosheng Tang, Lin Wang, Bo Feng
Glucagon-like peptide-1 (GLP-1) can protect arteriosclerotic lesions in apolipoprotein-E deficient (ApoE-/-) mice. Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) interaction serves a key role in the development of diabetic vascular complications. The present study examined whether the GLP-1 analogue liraglutide can ameliorate atherogenesis via inhibiting AGEs-induced RAGE expression. Male ApoE-/- mice (age, 10 weeks) were divided into control, GLP-1, AGEs and AGEs+GLP-1 group...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712893/the-glucagon-like-peptide-1-analogue-liraglutide-promotes-autophagy-through-the-modulation-of-5-amp-activated-protein-kinase-in-ins-1-%C3%AE-cells-under-high-glucose-conditions
#6
Xinyu Miao, Zhaoyan Gu, Yu Liu, Mengmeng Jin, Yanhui Lu, Yanping Gong, Lin Li, Chunlin Li
Glucagon-like peptide-1 (GLP-1) is a potent therapeutic agent for the treatment of diabetes and has been proven to protect pancreatic β-cells from glucotoxicity; however, its mechanisms of action are not entirely understood. Autophagy is a dynamic lysosomal degradation process that can protect organisms against metabolic stress. Studies have shown that autophagy plays a protective role in the survival of pancreatic β-cells under high glucose conditions. In the present study, we explored the role of autophagy in GLP-1-induced protection of pancreatic β-cells exposed to high glucose...
July 13, 2017: Peptides
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#7
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28701318/%C3%A2-liraglutide-for-weight-management
#8
(no author information available yet)
Since 1950, 25 anti-obesity drugs have been withdrawn from use across the world, largely as a result of adverse effects.(1) For several years, orlistat has been the only drug licensed in the UK for weight management.(2) In January 2017, a new presentation of the glucagon-like peptide-1 (GLP-1) analogue liraglutide (▾Saxenda - Novo Nordisk) was launched in the UK as an adjunct to a reduced-calorie diet and increased physical activity for weight management in adults. Here, we review the evidence for its efficacy and safety and consider its place in managing people who are overweight or obese...
July 2017: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/28694246/management-of-endocrine-disease-polycystic-ovary-syndrome-and-nonalcoholic-fatty-liver-disease
#9
REVIEW
Djuro Macut, Ivana Božić-Antić, Jelica Bjekić-Macut, Konstantinos Tziomalos
Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women, with a number of metabolic and reproductive consequences. Obesity, insulin resistance (IR) and type 2 diabetes are prominent metabolic characteristics of PCOS and common factors affecting liver function and generating nonalcoholic fatty liver disease (NAFLD). Multiple genes involved in the synthesis of androgens, cytokines and IR, as well as acquired factors, such as endocrine disruptors, could associate the etiopathogenesis of PCOS and NAFLD...
September 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28684145/glp-1-receptor-agonist-liraglutide-ameliorates-hepatosteatosis-induced-by-anti-cd3-antibody-in-female-mice
#10
Arata Itoh, Junichiro Irie, Hirotsune Tagawa, Yukie Kusumoto, Mari Kato, Nana Kobayashi, Kumiko Tanaka, Rieko Kikuchi, Masataka Fujita, Yuya Nakajima, Yuehong Wu, Satoru Yamada, Toshihide Kawai, William M Ridgway, Hiroshi Itoh
AIMS: Hepatosteatosis is mainly induced by obesity and metabolic disorders, but various medications also induce hepatosteatosis. The administration of anti-CD3 antibody was shown to induce hepatosteatosis, but changes in lipid and glucose metabolism remain unclear. We investigated the mechanism of hepatosteatosis induced by anti-CD3 antibody and the effects of glucagon-like peptide-1 (GLP-1) receptor agonist that was recently shown to affect immune function in metabolic disorders. METHODS: Anti-CD3 antibody was administered to female BALB/c and C...
June 1, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28681988/effect-of-liraglutide-on-ectopic-fat-in-polycystic-ovary-syndrome-a-randomized-clinical-trial
#11
Signe Frøssing, Malin Nylander, Elizaveta Chabanova, Jan Frystyk, Jens Juul Holst, Caroline Kistorp, Sven O Skouby, Jens Faber
Women with polycystic ovary syndrome (PCOS) were treated with the GLP-1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT), and the prevalence of nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled, randomized clinical trial 72 women with PCOS and BMI >25 kg/m(2) and/or insulin resistance were treated with liraglutide or placebo 1.8 mg/day (2:1) for 26 weeks. Liver fat content was assessed by (1) HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test...
July 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28681199/beneficial-effects-of-liraglutide-glp1-analog-in-the-hippocampal-inflammation
#12
Andre R C Barreto-Vianna, Marcia B Aguila, Carlos A Mandarim-de-Lacerda
The brain is very sensitive to metabolic dysfunctions induced by diets high in saturated fatty acids, leading to neuroinflammation. The liraglutide has been found to have neuroprotective effects. However, its neuroprotective action in a model of palmitate-induced neuroinflammation had not yet been evaluated. Mice were intracerebroventricular (ICV) infused with palmitate and received subcutaneous liraglutide. The hippocampal dentate gyrus and CA1 regions were analyzed (morphology and inflammation-related proteins in microglia and astrocyte by confocal microscopy)...
July 5, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28678550/the-safety-of-albiglutide-for-the-treatment-of-type-2-diabetes
#13
Marc S Rendell
Albiglutide is a marketed long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection. It has significantly less gastrointestinal side effects than other GLP-1 RAs in current use but does not improve HbA1c or promote weight loss to the same extent as competitor agents such as liraglutide. Area Covered: The safety of albiglutide is discussed. The review encompassed a search of PubMed and a thorough analysis of the European Union and US Food and Drug Administration approval documents. Expert Opinion: Unlike competitor agents, the gastrointestinal side effects of albiglutide are not much greater than placebo...
July 5, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28678048/antihyperglycemic-agents-and-cardiovascular-outcomes-recent-insights
#14
Harpreet S Bajaj, Bernard Zinman, Subodh Verma
PURPOSE OF REVIEW: To summarize cardiovascular outcome trials (CVOTs) with antihyperglycemic agents conducted since 2008 US Food and Drug Administration guidance. RECENT FINDINGS: A series of large CVOTs since 2008 have included patients with type 2 diabetes (T2D), who are otherwise treated according to standard of care. After the initial trials with incretin agents demonstrated cardiovascular safety, two recent CVOTs with currently available antihyperglycemic agents - EMPA-REG OUTCOME with empagliflozin and LEADER with liraglutide - show a significant reduction of the primary composite outcome, including a significant difference in the cardiovascular death end-point in both trials [EMPA-REG OUTCOME: hazard ratio = 0...
July 3, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28674957/a-review-of-the-long-term-efficacy-tolerability-and-safety-of-exenatide-once-weekly-for-type-2-diabetes
#15
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/28671791/-cardiovascular-protection-of-patients-with-type-2-diabetes-from-empa-reg-outcome-to-leader
#16
André J Scheen, Caroline Wallemacq, Bernard Jandrain, Philippe Ernest
Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively)...
August 24, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28668964/glp-1-glp-1r-signaling-in-regulation-of-adipocyte-differentiation-and-lipogenesis
#17
Jicui Chen, Huichen Zhao, Xiaoli Ma, Yuchao Zhang, Sumei Lu, Yangang Wang, Chen Zong, Dandan Qin, Yuanmei Wang, Yingfeng Yingfeng Yang, Xiangdong Wang, Yuantao Liu
BACKGROUND/AIMS: The aim of this study was to determine the direct role of liraglutide (LG) in adipogenesis and lipid metabolism. METHODS: Lipid accumulation was evaluated by oil red O staining, quantitative real-time PCR (qPCR) was performed to determine glucagon-like peptide 1 receptor (GLP-1R), fatty acid synthase (FASN) and adipose triglyceride lipase (ATGL) expression in 3T3-L1 preadipocytes, differentiated adipocytes and in adipose tissues from mice. The effects of LG on 3T3-L1 adipogenesis and lipid metabolism were analyzed with qPCR, Western Blotting, oil red O staining, immunohistochemistry (IHC) and immunofluorescence (IF)...
June 30, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28668697/xenopus-glp-1-inspired-discovery-of-novel-glp-1-receptor-agonists-as-long-acting-hypoglycemic-and-insulinotropic-agents-with-significant-therapeutic-potential
#18
Jing Han, Xinyu Chen, Yiyun Wang, Yingying Fei, Feng Zhou, Ying Zhang, Lin Liu, Pengbin Si, Junjie Fu
We here report the discovery and therapeutic efficacy of a novel series of glucagon-like peptide-1 (GLP-1) receptor agonists derived from Xenopus GLP-1. First, five amino acid-mutated Xenopus GLP-1s were synthesized, and xGLP-3 with the best acute and long-acting hypoglycemic activity was selected for further modification. Next, PEGylation of xGLP-3 was performed at specific sites, which were determined using cysteine mutagenesis scanning. Twelve PEGylated conjugates tethered with Mal-PEGs of 1, 2, and 5kDa were synthesized...
June 29, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28668144/a-practical-guide-to-the-use-of-glucose-lowering-agents-with-cardiovascular-benefit-or-proven-safety
#19
David Fitchett, Alice Cheng, Kim Connelly, Ronald Goldenberg, Shaun G Goodman, Lawrence A Leiter, Eva Lonn, Breay Paty, Paul Poirier, James Stone, David Thompson, Jean-Francois Yale, G B John Mancini
Patients with type 2 diabetes continue to have a high residual risk for cardiovascular events despite intensive risk factor modification. Recent clinical trials have shown that the antihyperglycemic agents empagliflozin and liraglutide reduce cardiovascular events. Other drugs have been shown to have cardiovascular safety. With glucose-lowering agents proven to reduce adverse cardiovascular outcomes, many cardiologists have begun to prescribe or recommend glucose-lowering agents. Other cardiologists are not yet comfortable with this role because they are not accustomed to initiating these drugs...
July 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28666800/a-novel-glp-1-gip-dual-agonist-is-more-effective-than-liraglutide-in-reducing-inflammation-and-enhancing-gdnf-release-in-the-mptp-mouse-model-of-parkinson-s-disease
#20
Ziyue Yuan, Dongfang Li, Peng Feng, Guofang Xue, Chenhui Ji, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD...
June 27, 2017: European Journal of Pharmacology
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