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LAR Exenatide

Panagiotis Anagnostis, Pavlos Siolos, Konstantinos Christou, Nifon K Gkekas, Nikoletta Kosmidou, Vasilios G Athyros, Asterios Karagiannis
Both type 1 and type 2 diabetes are associated with increased risk for cardiovascular disease (CVD) events. This risk seems to be reduced by achievement of euglycemia. However, after the withdrawal of rosiglitazone from the market, the question arose as to whether this risk concerns simply a matter of euglycemia or the distinct role played by each antidiabetic drug with respect to its effect on CVD risk. To address this issue, many studies have been published during the last decade involving old and new antidiabetic agents, which however yielded contradictory results...
March 2018: Hormones: International Journal of Endocrinology and Metabolism
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...
March 2018: Expert Opinion on Drug Safety
Sebastian Wiberg, Jesper Kjaergaard, Henrik Schmidt, Jakob Hartvig Thomsen, Martin Frydland, Matilde Winther-Jensen, Matias Greve Lindholm, Dan Eik Høfsten, Thomas Engstrøm, Lars Køber, Jacob Eifer Møller, Christian Hassager
OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm...
February 2018: Critical Care Medicine
Oliver Schnell, Lars Rydén, Eberhard Standl, Antonio Ceriello
In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications. Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk...
October 11, 2017: Cardiovascular Diabetology
Inka Miñambres, Antonio Pérez
Several GLP-1 receptor agonists are currently available for treatment of type 2 diabetic patients. Based on their pharmacokinetic/pharmacodynamic profile, these drugs are classified as short-acting GLP-1 receptor agonists (exenatide and lixisenatide) or long-acting GLP-1 receptor agonists (exenatide-LAR, liraglutide, albiglutide, and dulaglutide). In clinical practice, they are also classified as basal or prandial GLP-1 receptor agonists to differentiate between patients who would benefit more from one or another based on characteristics such as previous treatment and the predominance of fasting or postprandial hyperglycemia...
2017: Diabetology & Metabolic Syndrome
Martin Lorenz, Francesca Lawson, David Owens, Denis Raccah, Christine Roy-Duval, Anne Lehmann, Riccardo Perfetti, Lawrence Blonde
While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms)...
January 13, 2017: Cardiovascular Diabetology
Sonal Singh, Eugene E Wright, Anita Y M Kwan, Juliette C Thompson, Iqra A Syed, Ellen E Korol, Nathalie A Waser, Maria B Yu, Rattan Juneja
AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched...
February 2017: Diabetes, Obesity & Metabolism
X Xue, Z Ren, A Zhang, Q Yang, W Zhang, F Liu
BACKGROUND: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising results in the treatment of type 2 diabetes. Herein, we compared the efficacy and safety of once-weekly GLP-1RAs with exenatide and liraglutide separately. METHODS: We systematically surveyed the pertinent literature using various databases. The randomised controlled trials that compared once-weekly GLP-1RAs with exenatide and liraglutide in type 2 diabetes were included...
August 2016: International Journal of Clinical Practice
Kasper Kyhl, Jacob Lønborg, Niels Vejlstrup, Henning Kelbæk, Steffen Helqvist, Lene Holmvang, Erik Jørgensen, Kari Saunamäki, Hans Erik Bøtker, Peter Clemmensen, Lars Køber, Marek Treiman, Thomas Engstrøm
AIMS: We aimed to assess the effect of exenatide treatment as an adjunct to primary percutaneous coronary intervention (PCI) on long-term clinical outcome. METHODS AND RESULTS: We performed a post hoc analysis in 334 patients with a first STEMI included in a previous study randomised to exenatide (n=175) or placebo (n=159) as an adjunct to primary PCI. The primary endpoint was a composite of all-cause mortality and admission for heart failure during a median follow-up of 5...
July 20, 2016: EuroIntervention
Sebastian Wiberg, Christian Hassager, Jakob Hartvig Thomsen, Martin Frydland, Dan Eik Høfsten, Thomas Engstrøm, Lars Køber, Henrik Schmidt, Jacob Eifer Møller, Jesper Kjaergaard
BACKGROUND: Attenuating the neurological damage occurring after out-of-hospital cardiac arrest is an ongoing research effort. This dual-centre study investigates the neuroprotective effects of the glucagon-like-peptide-1 analogue Exenatide administered within 4 hours from the return of spontaneous circulation to comatose patients resuscitated from out-of-hospital cardiac arrest. METHODS/DESIGN: This pilot study will randomize a total of 120 unconscious patients with sustained return of spontaneous circulation after out-of-hospital cardiac arrest undergoing targeted temperature management in a blinded one-to-one fashion to a 6-hour and 15-minute infusion of either Exenatide or placebo...
June 30, 2016: Trials
Zhixia Li, Yuan Zhang, Xiaochi Quan, Zhirong Yang, Xiantao Zeng, Linong Ji, Feng Sun, Siyan Zhan
OBJECTIVE: To synthesize current evidence of the impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on hypoglycemia, treatment discontinuation and glycemic level in patients with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Literature search (Medline, Embase, the Cochrane library), website of clinical trial, bibliographies of published systematic reviews. ELIGIBILITY CRITERIA: Randomized controlled trials with available data comparing GLP-1 RAs with placebo or traditional anti-diabetic drugs in patients with type 2 diabetes...
2016: PloS One
Kira B Harris, Delilah J McCarty
Glucagon-like peptide-1 (GLP-1) has been evaluated for use in the treatment of type 2 diabetes mellitus (T2DM) due to its role in glucose regulation. Four GLP-1 receptor agonists (RAs) are currently indicated for T2DM in the USA. Exenatide and liraglutide are short-acting and require twice-daily and daily dosing, respectively. Two longer acting agents, exenatide long-acting release (LAR) and albiglutide, were formulated to allow for once-weekly dosing. All four GLP-1 RAs have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with first- and second-line diabetes agents including metformin, sulfonylureas, thiazolidinediones, and insulin...
February 2015: Therapeutic Advances in Endocrinology and Metabolism
Roberto Sierra Poyatos, Pilar Riobó Serván, Clotilde Vázquez Martínez
INTRODUCTION: GLP-1 analogs have been shown to be an effective treatment of type 2 diabetes mellitus (DM-2) and obesity. OBJECTIVES: Evaluate the efficacy of exenatide LAR on weight loss, glycemic control, blood pressure (BP) and lipid profile, in DM-2 and obesity. MATERIAL AND METHODS: Retrospective study of patients treated with exenatide LAR for 6 months. Demographic data (age, gender), anthropometric, fasting glucose, glycated hemoglobin (HbA1c), blood pressure and lipid profile were collected at baseline and at 6 months after treatment...
October 24, 2014: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
André J Scheen
The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic agents have limitations in patients with CKD, incretin-based therapies are increasingly used for the management of T2DM. This review analyses (1) the influence of CKD on the pharmacokinetics of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists; and (2) the efficacy/safety profile of these agents in clinical practice when prescribed in patients with both T2DM and CKD...
January 2015: Clinical Pharmacokinetics
A J Scheen
Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes. The microsphere technology permits a prolonged absorption of exenatide from the subcutaneous depot, which allows one injection per week instead of two injections per day with the initial formulation of exenatide (Byetta). The clinical development programme DURATION showed that exenatide 2 mg once weekly more markedly reduces glycated haemoglobin (HbA(1c)), with a similar weight loss but a better digestive tolerance profile (less nausea and vomiting after treatment initiation), compared with the twice daily 10 microg exenatide...
April 2014: Revue Médicale de Liège
Jacob Lønborg, Niels Vejlstrup, Henning Kelbæk, Lars Nepper-Christensen, Erik Jørgensen, Steffen Helqvist, Lene Holmvang, Kari Saunamäki, Hans Erik Bøtker, Won Yong Kim, Peter Clemmensen, Marek Treiman, Thomas Engstrøm
Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown. The objectives of this substudy were to evaluate the association between hyperglycemia and infarct size, myocardial salvage, and area at risk, and to assess the interaction between exenatide and hyperglycemia...
July 2014: Diabetes
Jacob Lønborg, Henning Kelbæk, Niels Vejlstrup, Hans Erik Bøtker, Won Yong Kim, Lene Holmvang, Erik Jørgensen, Steffen Helqvist, Kari Saunamäki, Christian Juhl Terkelsen, Mikkel Malby Schoos, Lars Køber, Peter Clemmensen, Marek Treiman, Thomas Engstrøm
BACKGROUND: Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined as time from first medical contact to first balloon. METHODS AND RESULTS: Patients with STEMI and Thrombolysis In Myocardial Infarction flow 0/1 were randomly assigned to intravenous exenatide or placebo continuous infusion...
April 2012: Circulation. Cardiovascular Interventions
C F Deacon, E Mannucci, B Ahrén
AIMS: During recent years, two strategies of incretin-based therapy [glucagon-like peptide-1 (GLP-1) receptor agonism and dipeptidyl peptidase-4 (DPP-4) inhibition] have entered the market for pharmacological management of type 2 diabetes. A main indication for this therapy is as add-on to on-going metformin therapy in subjects with type 2 diabetes who have insufficient glycaemic control with metformin alone. The aim of this study was to compare improvements in glycaemic control and changes in body weight, as well as adverse events, in comparable studies with incretin-based therapy as add-on to metformin...
August 2012: Diabetes, Obesity & Metabolism
Giuseppe Derosa, Pamela Maffioli
Recently incretin-based therapies have been developed in the clinical practice, this class includes both the dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin), and the glucagon-like peptide- 1 (GLP-1) receptor agonists [exenatide, exenatide long acting release (LAR) and liraglutide]. In particular exenatide and liraglutide have structural similarity and bind to the GLP-1 receptor, displaying a similar broad range of activities relevant to improving glycemic control, including stimulation of insulin secretion and reduction of glucagon secretion, both in a glucose-dependent manner...
August 2012: Current Clinical Pharmacology
Lars Wichmann Madsen, Jeffrey A Knauf, Carsten Gotfredsen, Andrew Pilling, Ingrid Sjögren, Søren Andersen, Lene Andersen, Anne Sietske de Boer, Katia Manova, Afsar Barlas, Sushil Vundavalli, Niels C Berg Nyborg, Lotte Bjerre Knudsen, Anne Marie Moelck, James A Fagin
Liraglutide and exenatide are glucagon-like peptide receptor (GLP-1R) agonists used in the treatment of type 2 diabetes. Both molecules have been associated with the development of thyroid C-cell tumors after lifetime exposure in rodents. Previously, it has been reported that these tumors are preceded by increased plasma calcitonin and C-cell hyperplasia. We can now document that the murine C-cell effects are mediated via GLP-1R. Thus, 13 wk of continuous exposure to GLP-1R agonists was associated with marked increases in plasma calcitonin and in the incidence of C-cell hyperplasia in wild-type mice...
March 2012: Endocrinology
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