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https://www.readbyqxmd.com/read/28418262/adherence-and-persistence-in-patients-with-type-2-diabetes-mellitus-newly-initiating-canagliflozin-dapagliflozin-dpp-4s-or-glp-1s-in-the-united-states
#1
Jennifer Cai, Victoria Divino, Chakkarin Burudpakdee
OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors were first approved in the US in 2013; therefore, real-world (RW) studies describing outcomes are limited. This retrospective study evaluated adherence and persistence among patients initiating canagliflozin (CANA), dapagliflozin (DAPA), GLP-1 agonists (GLP-1s) and DPP-4 inhibitors (DPP-4s) over a 12-month follow-up from a US managed care perspective. METHODS: Patients newly initiating CANA, DAPA, GLP-1s, or DPP-4s from 2/1/2014-6/30/2014 were identified from the QuintilesIMS PharMetrics Plus Database...
April 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28414465/topical-intestinal-aminoimidazole-agonists-of-g-protein-coupled-bile-acid-receptor-1-promote-glucagon-like-peptide-1-secretion-and-improve-glucose-tolerance
#2
Manuel Lasalle, Vanessa Hoguet, Nathalie Hennuyer, Florence Leroux, Catherine Piveteau, Loic Belloy, Sophie Lestavel, Emmanuelle Vallez, Emilie Dorchies, Isabelle Duplan, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Rajaa Boulahjar, Adrien Herledan, Bart Staels, Benoit Deprez, Anne Tailleux, Julie Charton
The role of the G-Protein-coupled Bile Acid Receptor TGR5 in various organs, tissues and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating Glucagon Like Peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability...
April 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28413961/incretins-and-lipid-metabolism
#3
Vasilis Tsimihodimos, Moses S Elisaf
Backgound: Recent findings indicate that incretin hormones and incretin-based therapies may affect the metabolism of lipoproteins, although the corresponding mechanisms are not clearly defined. OBJECTIVE: To summarize the available data on the mechanisms linking incretins with the characteristics of serum lipoproteins and discuss the clinical implications of these relationships. METHODS: PubMed was searched using the terms "incretins", "GLP-1", "GIP" and "lipids", "dyslipidemia", "triglycerides", "apolipoprotein B48"...
April 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28408435/neurturin-and-a-glp-1-analogue-act-synergistically-to-alleviate-diabetes-in-zucker-diabetic-fatty-rats
#4
James L Trevaskis, Chester Bittencourt Sacramento, Hani Jouihan, Safina Ali, John Le Lay, Stephanie Oldham, Nicholas Bhagroo, Brandon B Boland, Jennifer Cann, Yuan Chang, Terrence O'Day, Victor Howard, Christina Reers, Maria Sorhede Winzell, David M Smith, Michael Feigh, Pernille Barkholt, Kay Schreiter, Matthias Austen, Uwe Andag, Simon Thompson, Lutz Jermutus, Matthew P Coghlan, Joseph Grimsby, Cord Dohrmann, Christopher J Rhodes, Cristina M Rondinone, Arun Sharma
Neurturin (NRTN), a member of the glial-derived neurotrophic factor (GDNF) family, was identified from an embryonic chicken pancreatic cDNA library in a screen for secreted factors. Here, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a GLP-1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and β-cell mass, and prevented deterioration of islet organization...
April 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28407414/association-of-glucagon-like-peptide-1-receptor-agonist-glp-1-ra-use-and-rates-of-acute-myocardial-infarction-stroke-and-overall-mortality-in-patients-with-type-2-diabetes-mellitus-in-a-large-integrated-health-system
#5
Robert S Zimmerman, Todd M Hobbs, Brian J Wells, Sheldon X Kong, Michael W Kattan, Jon Bouchard, Kevin M Chagin, Changhong Yu, Brian Sakurada, Alex Milinovich, Wayne Weng, Janine M Bauman, Kevin M Pantalone
AIMS: To assess the potential impact of GLP-1 RA exposure on cardiovascular disease (CVD) and mortality outcomes in patients with type 2 diabetes (T2D), using a large retrospective cohort. MATERIALS AND METHODS: Patients with T2D between 2005-2014 (N = 105,862) were identified in the electronic health record system at Cleveland Clinic using a validated electronic phenotype. A time-dependent, Cox, multiple regression analysis was used to assess the association between GLP-1 RA exposure and risk of acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and overall mortality, as well as the composite of all three outcomes...
April 13, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#6
REVIEW
André J Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced...
March 25, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28395938/perceptions-of-general-practitioners-on-initiation-and-intensification-of-type-2-diabetes-injectable-therapies-a-quantitative-study-in-the-united-kingdom
#7
Daniel Sterzi, Sébastien Auziere, Divina Glah, Marie Markert Jensen
Most diabetes care is done by general practitioners (GPs) in the UK. This study aimed to determine GPs' comfort level in initiating and intensifying injectable therapies, identifying any associated barriers, and assessing reasons for referral to specialists. This web-interview included 128 general practitioners (GPs) experienced in type 2 diabetes (T2D) management, as well as 57 specialists and 30 nurses who were studied for secondary objectives. GPs felt more comfortable initiating the 1st injectable therapy - typically the glucagon-like peptide-1 receptor agonists (GLP-1 RA) - than the 2nd...
April 7, 2017: Primary Care Diabetes
https://www.readbyqxmd.com/read/28393583/spotlight-on-canagliflozin-300-review-of-its-efficacy-and-an-indirect-comparison-to-other-sglt-2-inhibitors-and-long-acting-glp-1-receptor-agonists
#8
Awadhesh Kumar Singh, Ritu Singh
Both sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been consistently found to lower blood glucose, body weight and systolic blood pressure (SBP) in patients with type 2 diabetes mellitus (T2DM). While all the SGLT-2Is inhibit glucose reabsorption by blocking SGLT-2 receptor in kidney, dose-dependently, the highest licensed dose of canagliflozin 300-mg has an additional ability to inhibit SGLT-1 receptor in intestine transiently, that may lead to additional inhibition of prandial glucose absorption, unlike other approved highly selective SGLT-2Is...
April 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28392300/glucagon-like-peptide-1-receptor-agonists-a-class-update-for-treating-type-2-diabetes
#9
REVIEW
Julie A Lovshin
Current management options for treating type 2 diabetes are diverse. Many different classes of antidiabetes therapies are used in clinic, and several new candidates are in late-phase clinical trial. This therapeutic abundance is a windfall for patients because it facilitates individualized patient care. Evidence-based positioning of these agents is challenging, however, requiring comprehensive and balanced familiarity with each drug class. In this review, I provide a clinical update of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of incretin-based, injectable antidiabetes therapies which improve fasting and postprandial blood glucose control through glucose-dependent pancreatic islet cell hormone secretion without significant risks for hypoglycemia...
April 5, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28387682/exendin-4-treatment-improves-lps-induced-depressive-like-behavior-without-affecting-pro-inflammatory-cytokines
#10
Filip Ventorp, Cecilie Bay-Richter, Analise Sauro Nagendra, Shorena Janelidze, Viktor Sjödahl Matsson, Jack Lipton, Ulrika Nordström, Åsa Westrin, Patrik Brundin, Lena Brundin
BACKGROUND: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration...
April 4, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28386912/neuropsychiatric-safety-with-liraglutide-3-0%C3%A2-mg-for-weight-management-results-from-randomized-controlled-phase-2-and-3a-trials
#11
P M O'Neil, V R Aroda, A Astrup, R Kushner, D C W Lau, T A Wadden, J Brett, A Cancino, J P H Wilding
AIMS: Liraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Due to concerns over the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc. METHODS: Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 kg/m(2) or ≥27 kg/m(2) with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3...
April 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28385659/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-sitagliptin-as-an-add-on-to-metformin-thiazolidinediones-or-both-in-patients-with-type-2-diabetes-sustain-2-a-56-week-double-blind-phase-3a-randomised-trial
#12
Bo Ahrén, Luis Masmiquel, Harish Kumar, Mehmet Sargin, Julie Derving Karsbøl, Sanja Hald Jacobsen, Francis Chow
BACKGROUND: Semaglutide is a novel glucagon-like peptide-1 (GLP-1) analogue, suitable for once-weekly subcutaneous administration, in development for treatment of type 2 diabetes. We assessed the efficacy and safety of semaglutide versus the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin, thiazolidinediones, or both. METHODS: We did a 56-week, phase 3a, randomised, double-blind, double-dummy, active-controlled, parallel-group, multinational, multicentre trial (SUSTAIN 2) at 128 sites in 18 countries...
April 3, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28383832/-cardiovascular-and-renal-protection-of-patients-with-type-2-diabetes-focus-after-empa-reg-outcome-and-leader
#13
REVIEW
A J Scheen, L Piérard, J-M Krzesinski, N Paquot
Type 2 diabetes (T2D), often associated with arterial hypertension, represents a high risk of cardiovascular disease and nephropathy. Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with T2D 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. Both medications showed a significant reduction in major cardiovascular events (-14 and -13 %, respectively), cardiovascular mortality (-38 and -22%), all-cause mortality (-32 and -15 %) and renal events (-39 et -22 %)...
September 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28368447/co-expressed-class-b-g-protein-coupled-secretin-and-glp-1-receptors-self-and-cross-associate-impact-on-pancreatic-islets
#14
Kaleeckal G Harikumar, Shannen Lau, Patrick M Sexton, Denise Wootten, Laurence J Miller
Class B GPCRs form symmetrical homo-dimeric complexes along the lipid face of transmembrane segment 4, and can form hetero-dimeric complexes, although their structure is unknown. The current study demonstrates that the lipid face of TM4 is also the predominant determinant for formation of hetero-receptor complexes between two class B receptors, secretin receptor (SecR) and glucagon-like peptide-1 receptor (GLP-1R), expressed on pancreatic islet cells. Since these receptors use the same interface for formation of homo- and hetero-receptor complexes, there might be competitive forces affecting expression of different complexes...
March 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28366815/liraglutide-suppression-of-caloric-intake-competes-with-the-intake-promoting-effects-of-a-palatable-cafeteria-diet-but-does-not-impact-food-or-macronutrient-selection
#15
Kellie M Hyde, Ginger D Blonde, Carel W le Roux, Alan C Spector
Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, is used as a treatment for Type 2 diabetes mellitus and obesity because it improves glycemia and decreases food intake. Here, we tested whether chronic activation of the GLP-1 receptor system with liraglutide would induce decreases in intake accompanied by changes in proportional food or macronutrient intake similar to those seen following RYGB in rats when a variety of palatable food options are available. A "cafeteria diet" was used that included: laboratory rodent chow, refried beans (low-fat/low-sugar), low-fat yogurt (low-fat/high-sugar), peanut butter (high-fat/low-sugar) and sugar-fat whip (high-fat/high-sugar)...
March 30, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28363772/characterization-of-signal-bias-at-the-glp-1-receptor-induced-by-backbone-modification-of-glp-1
#16
Marlies V Hager, Lachlan Clydesdale, Samuel H Gellman, Patrick M Sexton, Denise Wootten
The glucagon-like peptide-1 receptor (GLP-1R) is a cla B G protein-coupled receptor that is a major therapeutic target for the treatment of type 2 diabetes. Activation of this receptor promotes insulin secretion and blood glucose regulation. The GLP-1R can initiate signaling through several intracellular pathways upon activation by GLP-1. GLP-1R ligands that preferentially stimulate subsets among the natural signaling pathways ("biased agonists") could be useful as tools for elucidating the consequences of specific pathways and might engender therapeutic agents with tailored effects...
March 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28361843/does-combining-liraglutide-with-intragastric-balloon-insertion-improve-sustained-weight-reduction
#17
Mahmoud M Mosli, Moaiad Elyas
BACKGROUND/AIM: Intragastric balloon (IGB) is an effective and safe method of weight reduction. However, IGBs have been associated with a high rate of weight regain post removal. Accordingly, ways to improve sustained weight reduction including concomitant treatment with Glucagon-like peptide 1 (GLP-1) agonists have been proposed. This study aims to evaluate the effect of adding Liraglutide to IGB insertion on sustained weight reduction. PATIENTS AND METHODS: A retrospective analysis of all cases treated with IGB with or without Liraglutide was performed...
March 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28357715/no-dose-adjustment-is-recommended-for-digoxin-warfarin-atorvastatin-or-a-combination-oral-contraceptive-when-coadministered-with-dulaglutide
#18
Amparo de la Peña, Xuewei Cui, Jeanne Geiser, Corina Loghin
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of type 2 diabetes mellitus are known to delay gastric emptying (GE). The potential effect of the GLP-1 RA dulaglutide on the pharmacokinetics (PK) of four orally administered drugs and on the pharmacodynamic (PD) effect of warfarin was investigated. METHODS: In four separate clinical pharmacology studies, digoxin, warfarin, atorvastatin and Ortho-Cyclen(®) were orally administered to healthy subjects with and without a subcutaneous dose of dulaglutide 1...
March 29, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28355570/pancreatic-%C3%AE-cell-derived-glucagon-related-peptides-are-required-for-%C3%AE-cell-adaptation-and-glucose-homeostasis
#19
Shuyang Traub, Daniel T Meier, Friederike Schulze, Erez Dror, Thierry M Nordmann, Nicole Goetz, Norina Koch, Elise Dalmas, Marc Stawiski, Valmir Makshana, Fabrizio Thorel, Pedro L Herrera, Marianne Böni-Schnetzler, Marc Y Donath
Pancreatic α cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects of locally derived insulin secretagogues on β cell function and glucose homeostasis using mice with α cell ablation and with α cell-specific GLP-1 deficiency. Normally, intestinal GLP-1 compensates for the lack of α cell-derived GLP-1. However, upon aging and metabolic stress, glucose tolerance is impaired...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28349716/fixed-ratio-combination-therapy-with-glp-1-receptor-agonist-liraglutide-and-insulin-degludec-in-people-with-type-2-diabetes
#20
Lauge Østergaard, Christian Seerup Frandsen, Thomas Fremming Dejgaard, Sten Madsbad
A fixed combination of basal insulin degludec and glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (IDegLira; 50 units degludec/1.8 mg liraglutide) has been developed as a once daily injection for the treatment of type 2 diabetes (T2D). In the phase 3a trial programme "Dual action of liraglutide and insulin degludec in type 2 diabetes" (DUAL™), five trials of 26 weeks duration and one trial of 32 weeks duration have evaluated the efficacy and safety of IDegLira compared with administration of insulin degludec, insulin glargine, liraglutide alone or placebo...
March 28, 2017: Expert Review of Clinical Pharmacology
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