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Yushi Hirota, Tomokazu Matsuda, Shinsuke Nakajima, Michinori Takabe, Naoko Hashimoto, Tomoaki Nakamura, Yuko Okada, Kazuhiko Sakaguchi, Wataru Ogawa
PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are categorized as short- or long-acting types, but information regarding differences in the effects of these two types on postprandial glucose disposal has been limited. We have now investigated the effects of exenatide and liraglutide (short- and long-acting GLP-1RAs, respectively) on glucose disposal during an oral glucose tolerance test (OGTT). METHODS: Fourteen healthy volunteers with normal glucose tolerance underwent three OGTTs, which were performed without pharmacological intervention or after a single administration of exenatide or liraglutide at 30 min and 10 h, respectively, before test initiation...
November 8, 2018: Endocrine
Ying Li, Jintian He, Xiaolin Lyu, Yuan Yuan, Gaizhen Wang, Baohua Zhao
The aim of this research was to evaluate the potential of two chitosan (CS)-based hydrogel systems for nasal delivery of exenatide (EXT) in rats. Both of the EXT-loaded CS/glycerophosphate (GP)/CaCl2 (EXT/CS/GP/CaCl2 ) and EXT/CS/GP/MgCl2 hydrogel systems had similar in vitro release profiles. However, a difference in metal salt surprisingly resulted in multifaceted differences between the two hydrogel systems, such as EXT stability, gelation time, transepithelial transport, biodistribution and pharmacokinetics...
October 30, 2018: International Journal of Pharmaceutics
Guillaume Besch, Andrea Perrotti, Lucie Salomon du Mont, Marc Puyraveau, Xavier Ben-Said, Maude Baltres, Benoit Barrucand, Guillaume Flicoteaux, Lucie Vettoretti, Emmanuel Samain, Sidney Chocron, Sebastien Pili-Floury
BACKGROUND: The aim of the study was to investigate whether intravenous (iv) infusion of exenatide, a synthetic GLP-1 receptor agonist, could provide a protective effect against myocardial ischemia-reperfusion injury after coronary artery bypass graft (CABG) surgery. METHODS: A sub study analysis of patients > 18 years admitted for elective CABG and included in the ExSTRESS trial was conducted. Patients were randomized to receive either iv exenatide (1-h bolus of 0...
November 1, 2018: Cardiovascular Diabetology
Morgane Thomsen, Jens Juul Holst, Anna Molander, Kristian Linnet, Maurice Ptito, Anders Fink-Jensen
BACKGROUND: Preclinical studies in rodents have demonstrated inhibitory effects of glucagon-like peptide-1 (GLP-1) receptor stimulation on alcohol consumption. The effects of GLP-1 receptor stimulation on alcohol intake in primates have not been investigated. METHODS: We performed placebo-controlled studies on the effects of the GLP-1 receptor agonists exenatide and liraglutide on alcohol consumption in alcohol-preferring male African vervet monkeys. Monkeys selected for voluntary alcohol drinking were observed for at least 10 days of baseline drinking and allocated to drug or vehicle (n = 11-12 per group) balanced with respect to alcohol intake...
October 31, 2018: Psychopharmacology
Dilip Sharma, Suril Verma, Shivani Vaidya, Kiran Kalia, Vinod Tiwari
Glucagon-like peptide (GLP)-1 is an incretin hormone exhibiting several pharmacological actions such as neuroprotection, increased cognitive function, cardio-protection, decreased hypertension, suppression of acid secretion, increase in lyposis, and protection from inflammation. The most potent actions are glucose-dependent insulinotropic and glucagonostatic actions, stimulation of β-cell proliferation, enhanced insulin secretion and reduced weight gain in patients with type-2 diabetes pertaining to blood glucose control...
December 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Robert J Mentz, M Angelyn Bethel, Peter Merrill, Yuliya Lokhnygina, John B Buse, Juliana C Chan, João S Felício, Shaun G Goodman, Jasmine Choi, Stephanie M Gustavson, Nayyar Iqbal, Renato D Lopes, Aldo P Maggioni, Peter Öhman, Neha J Pagidipati, Neil R Poulter, Ambady Ramachandran, Barry Reicher, Rury R Holman, Adrian F Hernandez
Background In the EXSCEL (Exenatide Study of Cardiovascular Event Lowering), exenatide once-weekly resulted in a nonsignificant reduction in major adverse cardiovascular events ( MACEs ) and a nominal 14% reduction in all-cause mortality in 14 752 patients with type 2 diabetes mellitus (T2 DM ) with and without cardiovascular disease. Whether patients at increased risk for events experienced a comparatively greater treatment benefit with exenatide is unknown. Methods and Results In the EXSCEL population, we created risk scores for MACEs and all-cause mortality using step-wise selection of baseline characteristics...
October 2, 2018: Journal of the American Heart Association
C Ornelas, J Caiado, A Lopes, M C Pereira Dos Santos, M Pereira Barbosa
No abstract text is available yet for this article.
October 2018: Journal of Investigational Allergology & Clinical Immunology
Liat Soudry-Kochavi, Natalya Naraykin, Rosanna Di Paola, Enrico Gugliandolo, Alessio Peritore, Salvatore Cuzzocrea, Ehud Ziv, Taher Nassar, Simon Benita
One of the major disadvantages associated with macromolecules therapy is that most of them can only be administered parenterally. Exenatide, an efficient anti-diabetic drug, incretin mimetic, is currently administered subcutaneously (SC) causing compliance issues. Nanoparticles (NPs) are considered a promising solution for oral delivery of this drug. In order to overcome exenatide's inability to cross the enterocytes and to increase its stability in the gastrointestinal (GI) tract, we encapsulated exenatide into a nano-in-micro delivery system...
October 17, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Thorsten Otto, Melissa Myland, Heike Jung, Jeremie Lebrec, Hartmut Richter, Kirsi Norrbacka
Objective This retrospective database analysis complements previous research to understand treatment patterns for German patients newly initiating or switching to subsequent GLP-1 RAs. Methods Adult patients (≥18 years) initiating GLP-1 RA (Cohort 1 [C1]) or switching from a previous GLP-1 RA (Cohort 2 [C2]) to exenatide twice-daily (exBID), exenatide once-weekly (exQW), dulaglutide (DULA), or liraglutide (LIRA) were included in this analysis using IQVIA LRx from 01/01/2014-31/03/2017. Patients were required to have ≥1 oral antidiabetic prescription during the 6-month pre-index period and ≥12 months follow-up...
October 17, 2018: Current Medical Research and Opinion
Sanjay Kalra, Banshi Saboo
This review describes a recent advance in diabetes pharmacotherapeutics and drug delivery. ITCA 650 is an implantable device which delivers sustained and stable concentrations of the glucagon-like peptide 1 receptor agonist exenatide, when inserted subcutaneously. The article discusses the pharmacodynamics and pharmacokinetics of ITCA 650, and suggests how it's benefits can be utilized in clinical practice. It lists the advantages and limitations of the device, and shares tips for its rational use in type 2 diabetes care...
October 2018: JPMA. the Journal of the Pakistan Medical Association
Ting-Ting Yin, Yan Bi, Ping Li, Shan-Mei Shen, Wei-Min Wang, Can Jiang, Cai-Xia Gao, Yan Wang, Li-Jun Gao, Da-Long Zhu, Wen-Huan Feng
Background: Weight loss, especially fat mass reduction, helps to improve blood glucose control, insulin sensitivity, and β-cell function. This study aimed to compare the effect of exenatide and glargine on body composition in overweight and obese patients with type 2 diabetes (T2DM) who do not achieve adequate glycemic control with metformin. Methods: We performed a prospective, randomized study of 37 overweight or obese patients with T2DM who had inadequate glycemic control with metformin...
2018: Nutrition & Metabolism
Myfanwy C Geyer, Thomas Sullivan, Andrew Tai, Judith M Morton, Suzanne Edwards, A James Martin, Shiree J Perano, Lucia Gagliardi, Christopher K Rayner, Michael Horowitz, Jennifer J Couper
Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT. Six participants with CF and IGT were studied on 2 days, in a double-blind randomized crossover trial. After overnight fasting, they received exenatide 2.5 mcg or placebo (0.9% saline) subcutaneously 15 minutes before a pancake meal labelled with 13 C octanoate and pancreatic enzyme replacement...
September 26, 2018: Diabetes, Obesity & Metabolism
Yixing Li, Paul D Rosenblit
PURPOSE OF REVIEW: Mimetics and analogs that extend the half-life of native glucagon-like peptide-1 (GLP-1), i.e., glucagon-like peptide-1 receptor agonists (GLP-1 RAs), at therapeutic doses, are indicated as adjuncts to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). In patients with T2DM, GLP-1 RAs not only affect improvements in impaired beta cell and alpha cell function, suppress appetite, and induce weight loss but also possess multiple cardiovascular protective properties that potentially have a beneficial impact on atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality...
September 26, 2018: Current Cardiology Reports
Kayla Riswold, Valerie Flynn
No abstract text is available yet for this article.
September 2018: JAAD Case Reports
Sheila A Doggrell
Glucagon-like peptide-1 (GLP-1) is produced by the gut, stimulates insulin secretion from the pancreatic β-cells, and inhibits glucagon secretion from the α-cells. The GLP-1 receptor (GLP-1R) agonists are used in the treatment of type 2 diabetes (T2DM). Area covered: This review covers the clinical trials of the GLP-1R agonists (exenatide and liraglutide) and their potential as adjunct treatment in type 1 diabetes mellitus (T1DM). Expert opinion: GLP-1R agonists are unable to increase insulin secretion, in subjects with T1DM, who are C-peptide negative...
October 2018: Expert Opinion on Pharmacotherapy
Susan LaRue, Jane Springer, Michael Noderer, James Meehan, Carol H Wysham
BACKGROUND: Ease of injection is important to patients. An autoinjector was developed to deliver exenatide, a glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus. For autoinjection, 0.06-mm exenatide-containing microspheres are suspended in medium-chain triglycerides. Herein, we report design verification and usability testing of the autoinjector for exenatide once-weekly suspension (QWS) delivery. METHODS: Exenatide QWS in a single-chamber cartridge is self-injected subcutaneously with three main steps: mix, unlock, and inject...
September 20, 2018: Journal of Diabetes Science and Technology
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
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...
October 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
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
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
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