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https://www.readbyqxmd.com/read/29439603/semaglutide-in-type-2-diabetes-is-it-the-best-glucagon-like-peptide-1-receptor-agonist-glp-1r-agonist
#1
Sheila A Doggrell
Glucagon-like peptide-1 (GLP-1) is produced by the gut, and in a glucose-dependent manner stimulates insulin secretion while inhibiting glucagon secretion, reduces appetite and energy intake, and delays gastric emptying. The GLP-1R agonist semaglutide has recently been registered for use in the treatment of type 2 diabetes. Area covered: This review is of semaglutide in type 2 diabetes, and considers which properties of this GLP-1R agonist, may be responsible for its clinical outcome benefits in this condition...
February 13, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29424239/assessment-of-cardiovascular-risk-with-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes-using-an-alternative-measure-to-the-hazard-ratio
#2
Masayuki Kaneko, Mamoru Narukawa
BACKGROUND: Randomized clinical trials with the aim of evaluating the cardiovascular risks associated with glucagon-like peptide 1 (GLP-1) receptor agonists, lixisenatide, liraglutide, semaglutide, and exenatide, have been conducted. They showed different results among the agents, but the reason has not been explained. OBJECTIVE: To evaluate the cardiovascular risks associated with GLP-1 receptor agonists by using an alternative measure to the hazard ratio. METHODS: We used the difference in restricted mean survival time (RMST) as a measure of cardiovascular risks...
February 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29414148/exenatide-modulates-metalloproteinase-expression-in-human-cardiac-smooth-muscle-cells-via-the-inhibition-of-akt-signaling-pathway
#3
Enrique Gallego-Colon, Agnieszka Klych-Ratuszny, Agnieszka Kosowska, Wojciech Garczorz, Mohammad Reza F Aghdam, Michal Wozniak, Tomasz Francuz
BACKGROUND: Incretin analogue drugs, a FDA-approved treatment in diabetes, has been tested for its therapeutic properties as modulators of atherosclerosis. We investigated the effects of incretin drugs on the modulation of gene expression and protein levels of matrix metalloproteinases (MMPs) as well as their inhibitors - tissue inhibitors of metalloproteinases (TIMPs) in coronary artery smooth muscle cells (hCASMC) in the context of atherosclerotic plaque formation and inflammation. METHODS: TNFα-stimulated hCASMC were treated with Glucagon-like Peptide 1 (GLP-1) (10 nM and 100 nM) and Exendin-4 (1 nM and 10 nM)...
October 4, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29404511/exenatide-induces-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-expression-to-prevent-hepatic-steatosis
#4
Hilda E Ghadieh, Harrison T Muturi, Lucia Russo, Christopher C Marino, Simona S Ghanem, Saja S Khuder, Julie C Hanna, Sukanta Jash, Vishwajeet Puri, Garrett Heinrich, Cara Gatto-Weis, Kevin Y Lee, Sonia M Najjar
Exenatide, a glucagon-like peptide-1 receptor agonist, induces insulin secretion. Its role in insulin clearance has not been adequately examined. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance to maintain insulin sensitivity. Feeding C57BL/6J mice a high-fat diet down-regulates hepatic Ceacam1 transcription to cause hyperinsulinemia, insulin resistance, and hepatic steatosis, as in Ceacam1 null mice (Cc1-/- ). Thus, we tested whether exenatide regulates Ceacam1 expression in high-fat diet-fed mice and whether this contributes to its insulin sensitizing effect...
January 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29397532/changes-in-heart-rate-associated-with-exenatide-once-weekly-pooled-analysis-of-clinical-data-in-patients-with-type-2-diabetes
#5
Steven P Marso, Elise Hardy, Jenny Han, Hui Wang, Robert J Chilton
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. METHODS: A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10-30 weeks' duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups)...
February 3, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29394878/real-world-clinical-responses-in-patients-with-type-2-diabetes-mellitus-adding-exenatide-bid-ebid-or-mealtime-insulin-to-basal-insulin-a-retrospective-study-using-electronic-medical-record-data
#6
Kathleen Lang, Hiep Nguyen, Huan Huang, Elise Bauer, Philip Levin
AIM: Exenatide twice daily (EBID) and mealtime insulin are effective add-on therapies to basal insulin for type 2 diabetes patients in clinical trials. This study used electronic medical record (EMR) data to evaluate analogous real-world clinical responses. MATERIALS AND METHODS: Adult patients initiating EBID or mealtime insulin as add-on to basal insulin during January 2008 - March 2013 were identified in a U.S. EMR database. EBID patients were propensity score matched 1:1 to mealtime insulin patients...
February 2, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29386477/evaluation-of-drug-efficacy-of-glp-1-receptor-agonists-and-dpp-4-inhibitors-based-on-target-molecular-binding-occupancy
#7
Risa Takayanagi, Takumi Uchida, Koji Kimura, Yasuhiko Yamada
Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, exenatide, lixisenatide) have recently been used as anti-diabetes drugs. We examined relationships of the binding occupancy of GLP-1 receptors (Φ) and their clinical efficacy after administration of GLP-1 receptor agonists. Next, by focusing on changes of GLP-1 concentration after administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, alogliptin, sitagliptin, linagliptin), we analyzed the relationship between Φ and clinical efficacy...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29379894/long-acting-glp-1-receptor-agonist-exenatide-influence-on-the-autonomic-cardiac-sympatho-vagal-balance
#8
Vittorio Cacciatori, Giacomo Zoppini, Federico Bellavere, Riccardo Rigolon, Karl Thomaseth, Isabella Pichiri, Maddalena Trombetta, Marco Dauriz, Francesca De Santi, Giovanni Targher, Lorenza Santi, Enzo Bonora
Long-acting glucagon-like peptide 1 receptor agonists are increasingly used to treat type 2 diabetes. An increase of heart rate (HR) has been observed with their use. To elucidate the role of the cardiac sympatho-vagal balance as a possible mediator of the reported increase in HR, we performed power spectral analysis of HR variability (HRV) in patients receiving exenatide extended-release (ER). Twenty-eight ambulatory patients with type 2 diabetes underwent evaluation at initiation of exenatide-ER and thereafter at 3 and at 6 months...
January 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29372538/sustained-exenatide-delivery-via-intracapsular-microspheres-for-improved-survival-and-function-of-microencapsulated-porcine-islets
#9
Benjamin Lew, In-Yong Kim, Hyungsoo Choi, Kyekyoon Kevin Kim
The ability of glucagon-like peptide-1 analogs to enhance glucose-dependent insulin secretion and to inhibit β cell apoptosis could be of potential benefit for islet transplantation. In this study, we investigated the effect of sustained local delivery of exenatide, a synthetic exendin-4, on the in vitro viability and function of encapsulated porcine islets. Prior to encapsulation, we fabricated exenatide-loaded poly(latic-co-glycolic acid) microspheres, and investigated their release behavior with different initial drug-loading amounts...
January 25, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29346597/exenatide-increases-il-1ra-concentration-and-induces-nrf-2-keap-1-regulated-anti-oxidant-enzymes-relevance-to-%C3%AE-cell-function
#10
Paresh Dandona, Husam Ghanim, Sanaa Abuaysheh, Kelly Green, Sandeep Dhindsa, Antoine Makdissi, Manav Batra, Nitesh D Kuhadiya, Ajay Chaudhuri
Purpose: We have previously demonstrated anti-inflammatory and antioxidant effects of exenatide. We have now hypothesized that exenatide also increases the plasma concentration of IL-1RA, an endogenous anti-inflammatory protein and modulates the Nrf-2-Keap-1-ARE system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress. Methods: Twenty four obese type 2 diabetic patients on combined oral and insulin therapy were randomized to receive either exenatide 10μg or placebo b...
January 15, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29341461/effect-of-immediate-and-prolonged-glp-1-receptor-agonist-administration-on-uric-acid-and-its-kidney-clearance-post-hoc-analyses-of-four-clinical-trials
#11
Lennart Tonneijck, Marcel H A Muskiet, Mark M Smits, Petter Bjornstad, Mark H H Kramer, Michaela Diamant, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
AIMS: To determine effects of glucagon-like peptide (GLP)-1 receptor agonists (RA) on uric acid (UA)-levels and kidney UA-clearance. MATERIAL AND METHODS: Post-hoc analyses of four controlled clinical trials, which assessed actions of GLP-1RA-administration on kidney physiology. Immediate effects of GLP-1RA exenatide-infusion versus placebo was determined in 9 healthy overweight males (Study-A) and in 52 overweight T2DM-patients (Study-B). Effects were also examined of 12-week long-acting GLP-1RA liraglutide versus placebo in 36 overweight T2DM-patients (Study-C) and of 8-week short-acting GLP-1RA lixisenatide versus once-daily titrated insulin-glulisine in 35 overweight T2DM-patients (Study-D)...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29341370/real-world-clinical-outcomes-and-predictors-of-glycaemic-and-weight-response-to-exenatide-once-weekly-in-patients-with-type-2-diabetes-the-cibeles-project
#12
Juan José Gorgojo-Martínez, Manuel Angel Gargallo-Fernández, Miguel Brito-Sanfiel, Arturo Lisbona-Catalán
AIMS: To evaluate in a real-world setting the effectiveness of exenatide once-weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and weight response to this drug at 6 months. METHODS: Observational, retrospective, multicenter study in adult patients with T2D and BMI ≥30 kg/m2 from 4 tertiary Spanish hospitals who started ExQW therapy at least 6 months before the inclusion and had not achieved adequate glycaemic control on oral therapies or other GLP-1 receptor agonists...
January 17, 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29335533/fc-modified-exenatide-loaded-nanoparticles-for-oral-delivery-to-improve-hypoglycemic-effects-in-mice
#13
Yanan Shi, Xinfeng Sun, Liping Zhang, Kaoxiang Sun, Keke Li, Youxin Li, Qiang Zhang
To improve the oral efficiency of exenatide, we prepared polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w emulsion-solvent evaporation method. The particle size of the NPs-Fc was approximately 30 nm larger than that of the unmodified NPs with polydispersity indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest encapsulation efficiency of exenatide in the NPs was greater than 80%...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#14
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29331730/exenatide-exerts-cognitive-effects-by-modulating-the-bdnf-trkb-neurotrophic-axis-in-adult-mice
#15
Manuela Bomba, Alberto Granzotto, Vanessa Castelli, Noemi Massetti, Elena Silvestri, Lorella M T Canzoniero, Annamaria Cimini, Stefano L Sensi
Modulation of insulin-dependent signaling is emerging as a valuable therapeutic tool to target neurodegeneration. In the brain, the activation of insulin receptors promotes cell growth, neuronal repair, and protection. Altered brain insulin signaling participates in the cognitive decline seen in Alzheimer's disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates insulin secretion and, along with GLP-1 analogues, enhances neurotrophic signaling and counteracts cognitive deficits in preclinical models of neurodegeneration...
December 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29318537/glucose-control-and-weight-change-associated-with-treatment-with-exenatide-compared-with-basal-insulin-a%C3%A2-retrospective-study
#16
Christopher Ll Morgan, Qing Qiao, Susan Grandy, Kristina Johnsson, Sara Jenkins-Jones, Sarah Holden, Craig J Currie
INTRODUCTION: The aim of the study was to compare glycemic and weight change outcomes for type 2 diabetes patients treated with either exenatide once-weekly (EQW) or exenatide twice-daily (EBID) with those patients treated with basal insulin (BI). METHODS: Retrospective data (2010-2014) were extracted from the Clinical Practice Research Datalink, a UK primary care database. Patients previously naïve to injectable therapy initiating EQW, EBID, or BI were extracted and matched by propensity score within two analyses (EQW vs BI and EBID vs BI)...
January 9, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29316164/effects-of-exenatide-once-weekly-plus-dapagliflozin-exenatide-once-weekly-or-dapagliflozin-added-to-metformin-monotherapy-on-body-weight-systolic-blood-pressure-and-triglycerides-in-patients-with-type-2-diabetes-in-the-duration-8-study
#17
Serge A Jabbour, Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Peter Öhman
This post hoc analysis assessed the effects on cardiovascular risk factors of body weight, systolic blood pressure (SBP), and triglycerides after 28 weeks' treatment with exenatide once weekly (QW) plus dapagliflozin, as compared with exenatide QW or dapagliflozin, in patient subpopulations from the DURATION-8 trial of patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. Subgroups of patients were stratified according to their baseline body weight, SBP, and triglycerides...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29301824/clinical-impact-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-uncontrolled-type-2-diabetes-and-very-high-baseline-hba1c-the-freedom-1-hbl-study
#18
Robert R Henry, Julio Rosenstock, Douglas S Denham, Prakash Prabhakar, Lise Kjems, Michelle A Baron
OBJECTIVE: ITCA 650 is a subdermal osmotic mini-pump that continuously delivers exenatide subcutaneously for 3-6 months. The efficacy, safety, and tolerability of ITCA 650 added to diet and exercise alone or combined with metformin, sulfonylurea, or thiazolidinedione monotherapy or a combination of these drugs was evaluated in poorly controlled patients with type 2 diabetes (T2D) who were ineligible for participation in a placebo-controlled study (FREEDOM-1) because of severe hyperglycemia (HbA1c >10% [86 mmol/mol])...
January 4, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29286061/cardioprotection-by-exenatide-a-novel-mechanism-via-improving-mitochondrial-function-involving-the-glp-1-receptor-camp-pka-pathway
#19
Guanglei Chang, Jian Liu, Shu Qin, Youqin Jiang, Peng Zhang, Hui Yu, Kai Lu, Nan Zhang, Li Cao, Ying Wang, Yong Li, Dongying Zhang
Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) and its analogues exert cardioprotective effects via modulating cardiomyocyte metabolism. Mitochondria play a pivotal role in the regulation of cell metabolism. It was hypothesized that treatment with exenatide, a GLP-1 analogue, may exert cardioprotective effects by improving mitochondrial function in an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed to establish an in vitro model of H/R. Exenatide was added to the cells for 30 min prior to exposure to hypoxia...
December 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29283509/exenatide-exhibits-anti-inflammatory-properties-and-modulates-endothelial-response-to-tumor-necrosis-factor-%C3%AE-mediated-activation
#20
Wojciech Garczorz, Enrique Gallego-Colon, Agnieszka Kosowska, Agnieszka Kłych-Ratuszny, Michał Woźniak, Wiesław Marcol, K J Niesner, Tomasz Francuz
INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in the industrialized world. Incretin mimetic compounds such as exenatide are currently used in the treatment of type 2 diabetes. AIMS: We investigated the effects of incretin drugs on apoptosis, adhesion molecule expression, and concentration of extracellular matrix (ECM) metalloproteinases under inflammatory conditions within the context of atherosclerotic plaque formation of both human coronary artery endothelial cells (hCAECs) and human aortic endothelial cells (hAoECs)...
December 28, 2017: Cardiovascular Therapeutics
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