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https://www.readbyqxmd.com/read/28431666/glp-1-receptor-agonists-and-heart-failure-in-diabetes
#1
André J Scheen
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28421338/tailoring-pharmacotherapy-to-specific-eating-behaviours-in-obesity-can-recommendations-for-personalised-therapy-be-made-from-the-current-data
#2
Carl A Roberts, Paul Christiansen, Jason C G Halford
Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity...
April 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28417535/rates-of-hypoglycaemia-are-lower-in-patients-treated-with-insulin-degludec-liraglutide-ideglira-than-with-ideg-or-insulin-glargine-regardless-of-the-hypoglycaemia-definition-used
#3
P Norwood, R Chen, E Jaeckel, I Lingvay, H Jarlov, L Lehmann, S Heller
AIMS: The rates of hypoglycaemia reported in clinical trials are affected by the definitions of hypoglycaemia used. This post-hoc analysis took data from two trials comparing the once-daily, fixed ratio combination of insulin degludec/liraglutide (IDegLira) with basal insulin regimens, and re-analysed these data using alternative hypoglycaemia definitions and stratified outcomes by dosing time and baseline characteristics. MATERIALS AND METHODS: Post hoc analyses of the DUAL I (patients uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on insulin glargine (IGlar) U100) trials were carried out using different definitions of hypoglycaemia and by whether treatments were administered in the AM or PM...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28413990/effect-of-glucagon-like-peptide-1-receptor-agonists-on-all-cause-mortality-and-cardiovascular-outcomes-a-meta-analysis
#4
Shaylee Peterson, Arden Barry
BACKGROUND: Cardiovascular disease is the leading cause of death in patients with type 2 diabetes. OBJECTIVE: To assess the impact of glucagon-like peptide-1 receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant outcomes including all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart failure, in patients with type 2 diabetes. METHOD: EMBASE, MEDLINE, and CENTRAL were searched (inception to September 2016) for randomized, double-blind, placebo-controlled trials of at least one year in duration that compared any GLP1RA to placebo in patients with type 2 diabetes...
April 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28413872/favorable-effect-on-blood-volume-control-in-hemodialysis-patients-with-type-2-diabetes-after-switching-from-insulin-therapy-to-liraglutide-a-human-glucagon-like-peptide-1-analog-results-from-a-pilot-study-in-japan
#5
Masumi Kondo, Masao Toyoda, Moritsugu Kimura, Naoto Ishida, Masafumi Fukagawa
OBJECTIVE: Hemodialysis patients are advised to limit the intake of foods in order to control volume status and body weight (BW). We report the clinical course of five Japanese hemodialysis patients with type 2 diabetes mellitus (T2DM) who were switched from insulin to liraglutide, and the efficacy of the treatment, especially in terms of changes in interdialysis weight gain (IDWG). METHODS: This retrospective pilot study included 5 Japanese hemodialysis patients with T2DM...
April 20, 2017: Tokai Journal of Experimental and Clinical Medicine
https://www.readbyqxmd.com/read/28413488/the-effects-of-glp-1-analogues-on-pre-diabetes-of-the-children
#6
Qing-Xia Zhou, Zi-Yu Wang, Hua-Feng Zhao, Shan Wang
The aim of the study was to evaluate the clinical efficacy of glucagon-like peptide-1 (GLP-1) analogues in children of pre-diabetes to delay or reverse the development of pre-diabetes into the state of diabetes by early intervention. Prospective and randomized controlled clinical trials were performed in 42 cases of newly diagnosed pre-diabetes in children. The sample size was randomly divided into the two groups. The first group included 21 subjects comprising the lifestyle intervention group, i.e., control group, and the second group included 21 subjects comprising the lifestyle intervention+GLP-1 analogues liraglutide group, i...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28408435/neurturin-and-a-glp-1-analogue-act-synergistically-to-alleviate-diabetes-in-zucker-diabetic-fatty-rats
#7
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/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#8
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#9
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/28392927/liraglutide-for-weight-management-a-critical-review-of-the-evidence
#10
A Mehta, S P Marso, I J Neeland
OBJECTIVE: To review the efficacy, safety, and clinical applicability of liraglutide for weight management from phase III clinical trials. METHODS: A search of the English language literature was performed using PubMed search terms: "liraglutide", "glucagon-like peptide-1 receptor agonist", and "randomized clinical trial". Articles and bibliographies relevant to the subject were reviewed and additional references known to the authors were included. RESULTS: Five randomized, placebo-controlled trials of liraglutide for weight management were identified...
March 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/28392300/glucagon-like-peptide-1-receptor-agonists-a-class-update-for-treating-type-2-diabetes
#11
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/28387138/cardiovascular-safety-of-liraglutide-for-the-treatment-of-type-2-diabetes
#12
R A Chudleigh, Steve Bain
Liraglutide is a GLP-1 RA that is an option for treatment of T2DM. Typical of all new glucose-lowering agents, its CV safety profile is of great interest. Areas covered: This article outlines the efficacy of the GLP-1 RA liraglutide from RCTs, moving through the pivotal phase 3 LEAD trials, and subsequent meta-analyses to assess CV safety. This review describes evolution of regulatory requirements to obtain safety information through dedicated CVOTs. Expert opinion: Since the FDA mandated that CV outcomes for new diabetes therapies should be assessed via a dedicated CVOT, opinion of their utility in T2DM evolved from cynicism through to enthusiasm...
April 7, 2017: Expert Opinion on Drug Safety
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
#13
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/28383832/-cardiovascular-and-renal-protection-of-patients-with-type-2-diabetes-focus-after-empa-reg-outcome-and-leader
#14
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/28382596/liraglutide-improves-water-maze-learning-and-memory-performance-while-reduces-hyperphosphorylation-of-tau-and-neurofilaments-in-app-ps1-tau-triple-transgenic-mice
#15
Shuyi Chen, Jie Sun, Gang Zhao, Ai Guo, Yanlin Chen, Rongxia Fu, Yanqiu Deng
The purpose of this study was to explore how liraglutide affects AD-like pathology and cognitive function in APP/PS1/Tau triple transgenic (3 × Tg) Alzheimer disease (AD) model mice. Male 3 × Tg mice and C57BL/6 J mice were treated for 8 weeks with liraglutide (300 μg/kg/day, subcutaneous injection) or saline. Levels of phosphorylated tau, neurofilaments (NFs), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in brain tissues were assessed with western blots. Fluoro-Jade-B labeling were applied to detect pathological changes...
April 6, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28379427/tolerance-does-not-develop-toward-liraglutides-glucose-lowering-effect
#16
Tuuli Sedman, Eero Vasar, Vallo Volke
Context: Glucagon-like peptide-1 receptor agonists are popular antidiabetic drugs with potent glucose-lowering effects and low risk of hypoglycemia. Animal experiments and human data indicate that tolerance develops toward at least some of their effects, e.g., gastric motility. Whether tolerance develops toward the glucose-lowering effect of glucagon-like peptide-1 receptor agonists has never been formally tested. Objective: The objective of this pilot study was to test the hypothesis whether tolerance develops toward glucagon-like peptide-1 receptor agonists' glucose lowering effect in chronic use...
March 31, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28379024/-comments-on-current-guidelines-of-type-2-diabetes-mellitus-treatment
#17
Emil Martinka
In an effort to facilitate the widest possible application of recent findings in diabetology and the related medical fields, with regard to characteristics of medicines and current possibilities of using modern procedures, but also to their limitations due to the financial capacities of health insurance companies, SDS innovates its therapeutic recommendations for the treatment of diabetes mellitus on a regular basis. The most recent recommendations were issued by SDS in August 2016. The review discusses and describes several factors which the authors considered during their preparation: (1) Compliance with the findings of evidence-based medicine, compliance with reference recommendations (therapeutic recommendations ADA/EASD), compliance with summary characteristics of active substances in the treatment of diabetes mellitus and approved possibilities of their use, and compliance with indica-tive restrictions (IO) which define medical and economic conditions for health insurance covered treatment...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28378293/pharmacotherapy-of-obesity-clinical-trials-to-clinical-practice
#18
REVIEW
Kishore M Gadde, Y Pritham Raj
PURPOSE OF REVIEW: This review provides an overview of the current state of drug therapy for obesity, with a focus on four new drug therapies-lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide 3.0 mg-which have been approved by the US Food and Drug Administration (FDA) for long-term management of obesity since 2012. Topics discussed in this paper include rationale for pharmacotherapy, history of antiobesity drugs, and efficacy and safety data from randomized controlled trials with implications for clinical practice...
May 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28367916/analysis-of-efficacy-and-safety-of-dulaglutide-0-75-mg-stratified-by-sex-in-patients-with-type-2-diabetes-in-2-randomized-controlled-phase-3-studies-in-japan
#19
Yukiko Onishi, Tomonori Oura, Akiko Matsui, Jun Matsuura, Noriyuki Iwamoto
We analyzed the efficacy and safety of once weekly dulaglutide 0.75 mg by sex in 2 randomized, controlled phase 3 studies in Japanese patients with type 2 diabetes (a 52-week monotherapy study [comparator liraglutide 0.9 mg] and a 26-week combination therapy study [comparator insulin glargine]). Females comprised 18% of patients in the monotherapy study and 29% of patients in the combination therapy study. Mean reductions from baseline in glycated hemoglobin (HbA1c) were similar between the sexes for dulaglutide- and liraglutide-treated patients (range -1...
March 29, 2017: Endocrine Journal
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
#20
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
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