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https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#1
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/29239601/preparation-and-pharmaceutical-characterizations-of-lipidated-dimeric-xenopus-glucagon-like-peptide-1-conjugates
#2
Jing Han, Feng Zhou, Yingying Fei, Xinyu Chen, Junjie Fu, Hai Qian
Two glucagon-like peptide-1 (GLP-1) analogs (1 and 2) were synthesized by hybridizing the key sequences of GLP-1, exendin-4, lixisenatide and xenGLP-1B (Xenopus GLP-1 analog). To achieve long-acting hypoglycemic effects and to further improve their antidiabetic potencies, lipidization and dimerization strategies were used to afford two lipidated dimeric conjugates (9 and 11). Conjugates 9 and 11 showed stronger receptor activation potency than GLP-1 and exendin-4 in vitro. Moreover, 9 and 11 exhibited superior hypoglycemic and insulinotropic activities to liraglutide in db/db mice...
December 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29221659/cardiovascular-outcomes-with-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes-a-meta-analysis
#3
M Angelyn Bethel, Rishi A Patel, Peter Merrill, Yuliya Lokhnygina, John B Buse, Robert J Mentz, Neha J Pagidipati, Juliana C Chan, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Peter Öhman, Neil R Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez, Rury R Holman
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide. METHODS: In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke...
December 5, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29175324/lixisenatide-reduces-amyloid-plaques-neurofibrillary-tangles-and-neuroinflammation-in-an-app-ps1-tau-mouse-model-of-alzheimer-s-disease
#4
Hong-Yan Cai, Jun-Ting Yang, Zhao-Jun Wang, Jun Zhang, Wei Yang, Mei-Na Wu, Jin-Shun Qi
Type 2 diabetes mellitus (T2DM) has been identified as a high risk factor for Alzheimer's disease (AD). The impairment of insulin signaling has been found in AD brain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, normalises insulin signaling and acts as a neuroprotective growth factor. We have previously shown that the long-lasting GLP-1 receptor (GLP-1R) agonist lixisenatide plays an important role in memory formation, synaptic plasticity and cell proliferation of rats. In the follow-up study, we analysed the neuroprotective effect and mechanism of lixisenatide, injected for 60 days at 10 nmol/kg i...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29171021/xenopus-glp-1-derived-and-pegylated-glp-1-receptor-agonists-long-acting-hypoglycemic-and-insulinotropic-activities-with-potential-therapeutic-utilities
#5
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Ying Zhang, Lin Liu, Junjie Fu
BACKGROUND AND PURPOSE: Incretin-based therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists are effective methods for treating type 2 diabetes. Numerous research efforts are focused on the development of long-acting GLP-1 receptor agonists. However, all GLP-1 receptor agonists in clinical use or in clinical development are based on human GLP-1 or Gila GLP-1. We previously identified xGLP-1B as a potent GLP-1 receptor agonist based on Xenopus GLP-1. EXPERIMENTAL APPROACH: To further modify the structure of xGLP-1B, alanine scanning was performed to study the structure-activity relationship of xGLP-1B...
November 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29164973/an-indirect-treatment-comparison-of-the-efficacy-of-insulin-degludec-liraglutide-ideglira-and-insulin-glargine-lixisenatide-iglarlixi-in-patients-with-type-2-diabetes-uncontrolled-on-basal-insulin
#6
Marc Evans, Liana K Billings, Jonas Håkan-Bloch, Ulla Slothuus, Trine J Abrahamsen, Andreas Andersen, Jeroen P Jansen
AIMS: To obtain estimates of the relative treatment effects between insulin degludec/liraglutide (IDegLira) and insulin glargine U100/lixisenatide (iGlarLixi) in patients with type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin therapy. MATERIALS AND METHODS: Data from phase 3 trials providing evidence for estimating the relative efficacy and safety of IDegLira versus iGlarLixi in patients uncontrolled on basal insulin-only regimens were used in this analysis...
November 22, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/29143919/iglarlixi-reduces-glycated-hemoglobin-to-a-greater-extent-than-basal-insulin-regardless-of-levels-at-screening-post-hoc-analysis-of-lixilan-l
#7
Elisabeth Niemoeller, Elisabeth Souhami, Yujun Wu, Klaus H Jensen
INTRODUCTION: The treatment of patients with type 2 diabetes uncontrolled on basal insulin and oral glucose-lowering drugs was investigated previously in the LixiLan-L trial. In the LixiLan-L trial, patients experienced a 6-week run-in with insulin glargine U100 (iGlar) as part of the screening phase, followed by treatment with a fixed-ratio combination of iGlar + lixisenatide (iGlarLixi) or iGlar alone over 30 weeks. In the study reported here, we investigated the achievement of glycemic control in those who completed the 30-week LixiLan-L trial, as assessed by change in glycated hemoglobin (HbA1c) levels from screening, both for the overall category and for screening HbA1c subcategories...
November 16, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29107282/the-autonomic-nervous-system-and-cardiac-glp-1-receptors-control-heart-rate-in-mice
#8
Laurie L Baggio, John R Ussher, Brent A McLean, Xiemin Cao, M Golam Kabir, Erin E Mulvihill, Alexandra S Mighiu, Hangjun Zhang, Andreas Ludwig, Randy J Seeley, Scott P Heximer, Daniel J Drucker
OBJECTIVES: Glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine cells and exerts a broad number of metabolic actions through activation of a single GLP-1 receptor (GLP-1R). The cardiovascular actions of GLP-1 have garnered increasing attention as GLP-1R agonists are used to treat human subjects with diabetes and obesity that may be at increased risk for development of heart disease. Here we studied mechanisms linking GLP-1R activation to control of heart rate (HR) in mice...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29090600/comparison-between-insulin-degludec-liraglutide-treatment-and-insulin-glargine-lixisenatide-treatment-in-type-2-diabetes-a-systematic-review-and-meta-analysis
#9
Xiaoling Cai, Xueying Gao, Wenjia Yang, Linong Ji
AIM: To evaluate the efficacy and adverse effects of IDegLira and IGlarLixi treatment and to perform a comparison between two strategies. METHODS: The registration number is CRD42017053952. Randomized controlled trials of IGlarLixi treatment or IDegLira treatment compared with placebo or active hypoglycemic agents in type 2 diabetes were included. RESULTS: Eight trials were included. The absolute HbA1c change relative to baseline after IGlarLixi treatment was -1...
November 1, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29089722/lixisenatide-adlyxin-a-once-daily-incretin-mimetic-injection-for-type-2-diabetes
#10
Nicholas Leon, Richard LaCoursiere, Deirdre Yarosh, Roshni S Patel
Lixisenatide (Adlyxin), a once-daily incretin mimetic injection for type-2 diabetes.
November 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/29024408/effects-of-glucagon-like-peptide-1-receptor-agonists-on-cardiovascular-risk-factors-a-narrative-review-of-head-to-head-comparisons
#11
REVIEW
Niels B Dalsgaard, Tina Vilsbøll, Filip K Knop
Cardiovascular (CV) disease is the leading cause of death and morbidity in patients with type 2 diabetes. Five CV risk factors (blood pressure, resting heart rate, body weight, cholesterol levels and blood glucose) are monitored routinely as safety and efficacy endpoints in randomized clinical trials for diabetes therapies. To determine if different glucagon-like peptide-1 receptor agonists (GLP-1RAs) had varying effects on these CV risk factors, we reviewed 16 head-to-head trials directly comparing GLP-1RAs that included at least one of the five factors...
October 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28991932/addressing-unmet-needs-with-injectable-medications-in-type-2-diabetes-treatment-glucagon-like-peptide-1-receptor-agonists
#12
Steve V Edelman
Since 2005, four new GLP-1RAs (liraglutide, albiglutide, dulaglutide, and lixisenatide) and a once-weekly formulation of exenatide were approved for the treatment of persons with T2DM. Another GLP-1RA, semaglutide, is under review by the FDA, as is exenatide administered via an osmotic mini-pump.
October 2017: Journal of Family Practice
https://www.readbyqxmd.com/read/28945431/micellar-nanomedicine-of-novel-fatty-acid-modified-xenopus-glucagon-like-peptide-1-improved-physicochemical-characteristics-and-therapeutic-utilities-for-type-2-diabetes
#13
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Weiwei Zheng, Junjie Fu
To develop novel long-acting antidiabetics with improved therapeutic efficacy, two glucagon-like peptide-1 (GLP-1) analogs were constructed through the hybridization of key sequences of GLP-1, xenGLP-1B, exendin-4, and lixisenatide. Hybrids 1 and 2 demonstrated enhanced in vitro and in vivo biological activities and were further site-specifically lipidized at lysine residues to achieve prolonged duration of action and less frequent administration. Compared with their native peptides, compounds 3-6 showed similar in vitro activities but impaired in vivo acute hypoglycemic potencies due to decreased aqueous solubility and retarded absorption in vivo...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28932989/predictors-of-response-to-glucagon-like-peptide-1-receptor-agonists-a-meta-analysis-and-systematic-review-of-randomized-controlled-trials
#14
Matteo Monami, Ilaria Dicembrini, Besmir Nreu, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
AIMS: The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: A Medline and Embase search for "exenatide" OR "liraglutide" OR "albiglutide" OR "dulaglutide" OR "lixisenatide" was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs...
December 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28927992/protective-effects-of-the-glp-1-mimetic-exendin-4-in-parkinson-s-disease
#15
REVIEW
Dilan Athauda, Thomas Foltynie
There is increasing interest in the potential role of glucagon-like peptide-1 (GLP-1) receptor agonists as neuroprotective treatments in neurodegenerative diseases including Parkinson's disease following the publication of the results of the Exenatide-PD trial. Of the current GLP-1 receptor agonists already licensed to treat Type 2 diabetes several including exenatide, liraglutide and lixisenatide are the subject of ongoing clinical trials in PD. The underlying rationale for using drugs licensed and effective for T2DM in PD patients therefore needs to be scrutinized, and the results obtained to date critically reviewed...
September 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28925668/lixisenatide-adlyxin-for-type-2-diabetes-mellitus
#16
Valerie Niedermier, Gina Ayers, Sydney Springer
No abstract text is available yet for this article.
August 15, 2017: American Family Physician
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#17
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#18
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28748377/microvascular-effects-of-glucagon-like-peptide-1-receptor-agonists-in-type-2-diabetes-a-meta-analysis-of-randomized-controlled-trials
#19
Ilaria Dicembrini, Besmir Nreu, Alessia Scatena, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci, Matteo Monami
AIMS: Results with GLP1-receptor agonists (GLP-1RA) on microvascular complications of diabetes are contrasting. In trials designed for cardiovascular outcomes, both liraglutide and semaglutide were associated with a relevant reduction in the incidence and progression of nephropathy. On the other hand, in the same trials, semaglutide was associated with an increased progression of retinopathy, and a similar trend was observed for liraglutide. This meta-analysis is aimed at assessing the effects of GLP-1RA on retinopathy and nephropathy...
October 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28742225/the-efficacy-and-safety-of-lixisenatide-in-a-predominantly-asian-population-with-type-2-diabetes-insufficiently-controlled-with-basal-insulin-the-getgoal-l-c-randomized-trial
#20
W Yang, K Min, Z Zhou, L Li, X Xu, D Zhu, A Venkateshwar Rao, L S Murthy, N Zhang, I Li, E Niemoeller, S Shang
AIMS: To assess the effects on glycaemic control of lixisenatide versus placebo as add-on treatment to basal insulin (BI) ± metformin on glycated haemoglobin (HbA1c) reduction in patients with insufficiently controlled type 2 diabetes (T2D). METHODS: Patients (n = 448) with inadequately controlled T2D were randomized (1:1) to lixisenatide or placebo as add-on to BI ± metformin for 24 weeks after an 8-week run-in phase, during which BI was titrated to a target self-monitored plasma glucose (SMPG; 4...
July 25, 2017: Diabetes, Obesity & Metabolism
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