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https://www.readbyqxmd.com/read/30195966/semaglutide-review-and-place-in-therapy-for-adults-with-type-2-diabetes
#1
REVIEW
Ronald M Goldenberg, Oren Steen
Guidelines increasingly highlight the importance of multifactorial management in type 2 diabetes, in contrast to the more traditional focus on glycemic control. Semaglutide, a recently approved glucagon-like peptide-1 receptor agonist, is indicated in Canada for adults with type 2 diabetes to improve glycemic control as monotherapy with diet and exercise when metformin is inappropriate or as an add-on to either metformin alone or metformin plus a sulfonylurea or basal insulin. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trial program for semaglutide comprises 6 pivotal global phase 3a trials (SUSTAIN 1 through 6) and 2 Japanese phase 3a trials...
June 5, 2018: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/30194947/an-intestinal-paracellular-pathway-biased-toward-positively-charged-macromolecules
#2
Khaled Almansour, Alistair Taverner, Jerrold R Turner, Ian M Eggleston, Randall J Mrsny
Lacking an effective mechanism to safely and consistently enhance macromolecular uptake across the intestinal epithelium, prospects for successful development of oral therapeutic peptide drugs remain unlikely. We previously addressed this challenge by identifying an endogenous mechanism that controls intestinal paracellular permeability that can be activated by a peptide, termed PIP 640, which can increase cellular levels of phosphorylated myosin light chain at position S19 (MLC-pS19 ). Apical application in vitro or luminal application in vivo was shown to increase macromolecular solute transport within minutes that recovered completely within a few hours after removal...
September 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30187620/glucagon-like-peptide-1-receptor-agonists-for-antipsychotic-associated-cardio-metabolic-risk-factors-a-systematic-review-and-individual-participant-data-meta-analysis
#3
Dan Siskind, Margaret Hahn, Christoph U Correll, Anders Fink-Jensen, Anthony W Russell, Nikolaj Bak, Brian V Broberg, Julie Larsen, Pelle L Ishøy, Tina Vilsbøll, Filip K Knop, Steve Kisely, Bjørn H Ebdrup
OBJECTIVE: Patients with schizophrenia have higher cardio-metabolic risk, partially from antipsychotic-induced weight-gain. Glucagon-like-peptide-1 receptor-agonists (GLP-1RAs) may reduce antipsychotic-associated weight-gain, however, safety and efficacy in schizophrenia has not been systematically reviewed. MATERIALS AND METHODS: We systematically searched PubMed/EMBASE/PsycINFO/Cochrane, using the search terms "(antipsychotic and GLP-1RA)". Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed...
September 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/30165844/valuing-injection-frequency-and-other-attributes-of-type-2-diabetes-treatments-in-australia-a-discrete-choice-experiment
#4
Simon Fifer, John Rose, Kim K Hamrosi, Dan Swain
BACKGROUND: Multiple pharmacotherapy options are available to control blood glucose in Type 2 Diabetes Mellitus (T2DM). Patients and prescribers may have different preferences for T2DM treatment attributes, such as mode and frequency of administration, based on their experiences and beliefs which may impact adherence. As adherence is a pivotal issue in diabetes therapy, it is important to understand what patients value and how they trade-off the risks and benefits of new treatments. This study aims to investigate the key drivers of choice for T2DM treatments, with a focus on injection frequency, and explore patients' associated willingness-to-pay...
August 30, 2018: BMC Health Services Research
https://www.readbyqxmd.com/read/30156747/glucagon-like-peptide-1-receptor-agonists-in-type-2-diabetes-treatment-are-they-all-the-same
#5
REVIEW
Raffaella Gentilella, Valeria Pechtner, Antonella Corcos, Agostino Consoli
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an important class of drugs with a well-established efficacy and safety profile in patients with type 2 diabetes mellitus (T2DM). Agents in this class are derived from either exendin-4 (a compound present in Gila monster venom) or modifications of human GLP-1 active fragment. Differences among these drugs in duration of action (i.e. short-acting vs long-acting), effects on glycaemic control and weight loss, immunogenicity, tolerability profiles and administration routes offer physicians several options when selecting the most appropriate agent for individual patients...
August 29, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/30156447/health-related-quality-of-life-assessments-with-once-weekly-glucagon-like-peptide-1-receptor-agonists-in-type-2-diabetes-mellitus
#6
Liana K Billings, Yehuda Handelsman, Michael Heile, Doron Schneider, Kathleen Wyne
Type 2 diabetes (T2DM) is associated with significant impairment in health-related quality of life (HRQoL). A patient-centered collaborative approach is recommended to optimize clinical outcomes, including HRQoL, in this patient population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide effective glycemic control and have demonstrated beneficial effects on HRQoL and treatment satisfaction. Available once-weekly GLP-1 RAs may offer enhanced convenience compared with daily GLP-1 RAs and include exenatide extended-release (ER), dulaglutide, and semaglutide...
September 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/30156446/cardiovascular-outcomes-with-once-weekly-glp-1-ras-clinical-and-economic-implications
#7
Michael Heile, Kathleen Wyne, Liana K Billings, Anthony Cannon, Yehuda Handelsman, Michael Shannon
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects...
September 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/30156445/glycemic-efficacy-weight-effects-and-safety-of-once-weekly-glucagon-like-peptide-1-receptor-agonists
#8
Yehuda Handelsman, Kathleen Wyne, Anthony Cannon, Michael Shannon, Doron Schneider
This article provides an overview of the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic GLP-1 receptors, which increases insulin secretion, delays gastric emptying, and increases satiety. As a class, GLP-1 RAs lower A1c levels and have been associated with reductions in weight and blood pressure and reduced fluctuations in glucose levels, and they have a low risk of hypoglycemia. Exenatide extended release (ER) and dulaglutide monotherapy have shown similar or superior reductions in A1c and weight compared with various oral antidiabetic drugs (OADs)...
September 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/30145806/efficacy-of-different-antidiabetic-drugs-based-on-metformin-in-the-treatment-of-type-2-diabetes-mellitus-a-network-meta-analysis-involving-eight-eligible-randomized-controlled-trials
#9
Yan Peng, Shu-Hong Chen, Xiao-Nan Liu, Qing-Yun Sun
Diabetes mellitus is one of the most prevalent metabolic diseases globally and it is increasing in prevalence. It is one of the most expensive diseases with respect to total health care costs per patient as a result of its chronic nature and its severe complications. To provide a more effective treatment of type 2 diabetes mellitus (T2DM), this study aims to compare different efficacies of six kinds of hypoglycemic drugs based on metformin, including glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin, in T2DM by a network meta-analysis that were verified by randomized-controlled trials (RCTs)...
August 26, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30120857/mitral-cells-and-the-glucagon-like-peptide-1-receptor-the-sweet-smell-of-success
#10
Enrico Bagnoli, Una FitzGerald
The olfactory bulb (OB) is often affected at very early stages of neurodegenerative disorders, in the so-called "prodromal" phase. In Parkinson's disease (PD), olfactory disturbances appear years before motor symptoms arise. Additionally, pathological alpha-synuclein aggregates are found in olfactory regions before spreading to other areas of the brain. Being positioned at the frontier between the brain and a potentially hostile environment, could explain the particular vulnerability of the OB. Mitral cells (MCs), the principal projecting neurons of the olfactory system, are involved in the pathogenesis and in the prion-like progression of PD...
August 18, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/30115742/cardiovascular-benefits-of-glp-1-agonists-in-type-2-diabetes-a-comparative-review
#11
REVIEW
James G Boyle, Rachel Livingstone, John R Petrie
Type 2 diabetes (T2D) carries risks of both cardiovascular (CV) (myocardial infarction, stroke, and peripheral vascular disease) and microvascular (retinopathy/nephropathy/neuropathy) complications. Glucose-lowering is an effective strategy for preventing microvascular complications, but the extent to which it can reduce CV complications is less certain. Glucagon-like peptide-1 (GLP-1) agonists are potent glucose-lowering agents but also have potentially beneficial effects on other traditional (body weight, blood pressure (BP), and LDL cholesterol) and non-traditional risk factors (low grade inflammation and endothelial dysfunction)...
August 16, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/30104246/glucagon-like-peptide-1-and-its-cleavage-products-are-renoprotective-in-murine-diabetic-nephropathy
#12
Moellmann Julia, Klinkhammer Barbara Mara, Onstein Julia, Stöhr Robert, Jankowski Vera, Jankowski Joachim, Lebherz Corinna, Tacke Frank, Marx Nikolaus, Boor Peter, Lehrke Michael
Incretin based therapies, including GLP-1 receptor agonists and dipeptidylpeptidase 4 (DPP-4) inhibitors, are potent glucose lowering drugs. Still, only GLP-1 receptor agonists with close peptide homology to GLP-1 (liraglutide and semaglutide) but neither exenatide based GLP-1 receptor agonists nor DPP-4 inhibitors were found to reduce cardiovascular events. This different response might relate to GLP-1 receptor independent actions of GLP-1 caused by cleavage products only liberated by GLP-1 receptor agonists with close peptide structure to GLP-1...
August 13, 2018: Diabetes
https://www.readbyqxmd.com/read/30083774/glucagon-like-peptide-1-receptor-agonists-and-fracture-risk-a-network-meta-analysis-of-randomized-clinical-trials
#13
Y S Zhang, W Y Weng, B C Xie, Y Meng, Y H Hao, Y M Liang, Z K Zhou
Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433). INTRODUCTION: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients...
August 6, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/30082326/safety-and-efficacy-of-exenatide-once-weekly-plus-dapagliflozin-once-daily-versus-exenatide-or-dapagliflozin-alone-in-patients-with-type-2-diabetes-inadequately-controlled-with-metformin-monotherapy-52-week-results-of-the-duration-8-randomized-controlled-trial
#14
Serge A Jabbour, Juan P Frìas, Elise Hardy, Azazuddin Ahmed, Hui Wang, Peter Öhman, Cristian Guja
OBJECTIVE: Among patients with type 2 diabetes uncontrolled with metformin, exenatide once weekly (QW) plus dapagliflozin combination produced greater reductions in glycemia, weight, and systolic blood pressure (SBP) at 28 weeks than exenatide QW or dapagliflozin alone (DURATION-8). Here, we investigated the safety and maintenance of efficacy at 52 weeks, after a 24-week extension. RESEARCH DESIGN AND METHODS: This phase 3, multicenter, double-blind study randomized adults with type 2 diabetes (glycated hemoglobin [HbA1c ] 8...
August 6, 2018: Diabetes Care
https://www.readbyqxmd.com/read/30078011/pharmacological-signatures-of-the-exenatide-nanoparticles-complex-against-myocardial-ischemia-reperfusion-injury
#15
Yi Zhang, Ping Qian, Hong Zhou, Ruilin Shen, Bo Hu, Yajun Shen, Xiaofang Zhang, Xiaohua Shen, Guangtao Xu, Limin Jin
BACKGROUND/AIMS: Myocardial ischemia/reperfusion (I/R) injury (MI/RI) is a critical cause of death in patients with heart disease. However, the pharmaco-therapeutical outcome for MI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering myocardial function in MI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of exenatide-loaded poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) nanoparticles (NPs) against MI/RI...
August 3, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/30047216/impact-on-hba1c-and-body-weight-of-switching-from-other-glp-1-receptor-agonists-to-semaglutide-a-model-based-approach
#16
Rune V Overgaard, Søren Ø Lindberg, Desirée Thielke
AIMS: Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue approved for the treatment of type 2 diabetes. The impact of switching treatment from another GLP-1 receptor agonist (GLP-1RA) to semaglutide was investigated by analyses of exposure-response models. METHODS: HbA1c and body weight time-course models were developed, using up to 30 weeks of observations from four trials in the semaglutide phase 3 programme. Given the recommended dosing for each GLP-1RA, pharmacokinetic profiles were simulated based on published population pharmacokinetic models and exposure was adjusted by the relative potencies to ensure that model predictions matched the effects observed in clinical trials...
July 25, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/30041153/a-liquid-chromatography-high-resolution-mass-spectrometry-in-vitro-assay-to-assess-metabolism-at-the-injection-site-of-subcutaneously-administered-therapeutic-peptides
#17
Simone Esposito, Maria Lucia de Leonibus, Raffaele Ingenito, Elisabetta Bianchi, Laura Orsatti, Edith Monteagudo
Subcutaneous (SC) injection is the most common administration route for peptide therapeutics. Catabolism at the injection site can be a specific and major degradation pathway for many SC administered peptides. In some cases, it can significantly affect pharmacokinetics, particularly bioavailability, and have detrimental effects on the efficacy of the drug. This work describes a liquid chromatography-high resolution mass spectrometry based in vitro assay to assess peptide metabolism in the SC tissue (SCiMetPep assay)...
September 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
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
#18
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
#19
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
#20
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...
October 2018: Domestic Animal Endocrinology
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