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https://www.readbyqxmd.com/read/28929319/a-practical-approach-to-hypertension-management-in-diabetes
#1
REVIEW
Altamash Shaikh
Hypertension is one of the most important comorbidities of diabetes, contributing significantly to death and disability and leads to macrovascular and microvascular complications. When assessing the medical priorities for patients with diabetes, treating hypertension should be a primary consideration. Practical approaches to hypertension in diabetes, including individualized targets are discussed, as per stage and complication of diabetes, according to current studies and guidelines. Angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBs) are the most effective drugs for treating hypertension in diabetes, in the absence of contraindications...
September 19, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28860072/oral-delivery-of-a-therapeutic-gene-encoding-glucagon-like-peptide-1-to-treat-high-fat-diet-induced-diabetes
#2
Md Nurunnabi, Seung-Ah Lee, Vishnu Revuri, Yong Hwa Hwang, Sung Hun Kang, Minhyung Lee, Sungpil Cho, Kwang Jae Cho, Youngro Byun, You Han Bae, Dong Yun Lee, Yong-Kyu Lee
The number of people suffering from insulin-independent type 2 diabetes mellitus (T2DM) is ever increasing on a yearly basis. Current anti-diabetic medications often result in adverse weight gain and hypoglycemic episodes. Hypoglycemia can be avoided with glucagon-like peptide (GLP)-1 receptor agonists, which are expensive and require daily injections that may result immune activation. This study demonstrates the use of non-viral vector based oral delivery of GLP-1 gene through enterohepatic recycling pathways of bile acids...
August 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28801475/understanding-the-gap-between-efficacy-in-randomized-controlled-trials-and-effectiveness-in-real-world-use-of-glp-1ra-and-dpp4-therapies-in-patients-with-type-2-diabetes
#3
Ginger S Carls, Edward Tuttle, Ruo-Ding Tan, Johnny Huynh, John Yee, Steven V Edelman, William H Polonsky
OBJECTIVE: This objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide-1 receptor agonist (GLP-1RA) or dipeptidyl peptidase-4 inhibitor (DPP4) with published findings from randomized controlled trials (RCTs) evaluating these drugs...
August 11, 2017: Diabetes Care
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
#4
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...
July 27, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28676027/the-co-existence-of-nash-and-chronic-kidney-disease-boosts-cardiovascular-risk-are-there-any-common-therapeutic-options
#5
Marianna Papademetriou, Vasilios G Athyros, Eleni Geladari, Michael Doumas, Costas Tsioufis, Vasilios Papademetriou
Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease. NAFLD may evolve to non-alcoholic steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD) mortality. There is no generally accepted effective treatment for NAFLD/NASH. Chronic kidney disease (CKD) is relatively common and might co-exist with NAFLD/NASH, aggravate one another, and increase CVD risk. Common therapies could improve outcome. Potent statins at high doses, such as atorvastatin and rosuvastatin, ameliorate NAFLD/NASH and reduce the mortality rates by half as compared with those on the same statins but without liver disease...
June 20, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28479155/treatment-with-glp1-receptor-agonists-reduce-serum-crp-concentrations-in-patients-with-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#6
REVIEW
Mohsen Mazidi, Ehsan Karimi, Peyman Rezaie, Gordon A Ferns
AIM: To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations. METHOD: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched for the period up until March 16, 2016. Prospective studies evaluating the impact of GLP-1 RAs on serum CRP were identified. A random effects model (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis...
July 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28473214/diabetes-medications-and-cardiovascular-outcomes-in-type-2-diabetes
#7
REVIEW
Cecilia Chi, Jennifer Snaith, Jenny E Gunton
INTRODUCTION: Patients with type 2 diabetes have an increased risk of developing adverse cardiovascular (CV) outcomes. The evidence relating to the effects of glucose-lowering medications on CV outcomes is of variable quality and there are numerous trials ongoing. RESULTS: In this review, we summarise the available literature on CV outcomes of the following diabetes treatments: metformin, the sulfonylureas, acarbose, glucagon-like peptide 1 (GLP1) receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i), thiazolidinediones (TZDs) and insulin...
April 10, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28357772/switch-to-combined-glp1-receptor-agonist-lixisenatide-with-basal-insulin-glargine-in-poorly-controlled-t2dm-patients-with-premixed-insulin-therapy-a-clinical-observation-and-pilot-study-in-nine-patients
#8
Jürgen Harreiter, Lana Kosi-Trebotic, Albert Lukas, Peter Wolf, Yvonne Winhofer, Anton Luger, Alexandra Kautzky-Willer, Michael R Krebs
INTRODUCTION: To prove the feasibility and safety of a conversion to once-daily injected GLP1 agonist (lixisenatide) and long-acting basal insulin analogue (glargine) in patients with T2DM and poorly controlled glycemia previously treated with multiple injections of premixed insulins (iPremix) in an outpatient setting. METHODS: Nine patients with T2DM currently receiving iPremix formulations and poor glycemic control were switched to once-daily injected lixisenatide (Lixi) and basal insulin analogue glargine (iGlar) for a 12-week period...
June 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28292762/gpr40-reduces-food-intake-and-body-weight-through-glp-1
#9
Judith N Gorski, Michele J Pachanski, Joel Mane, Christopher W Plummer, Sarah Souza, Brande S Thomas-Fowlkes, Aimie M Ogawa, Adam B Weinglass, Jerry Di Salvo, Boonlert Cheewatrakoolpong, Andrew D Howard, Steven L Colletti, Maria E Trujillo
G protein-coupled receptor 40 (GPR40) partial agonists lower glucose through the potentiation of glucose-stimulated insulin secretion, which is believed to provide significant glucose lowering without the weight gain or hypoglycemic risk associated with exogenous insulin or glucose-independent insulin secretagogues. The class of small-molecule GPR40 modulators, known as AgoPAMs (agonist also capable of acting as positive allosteric modulators), differentiate from partial agonists, binding to a distinct site and functioning as full agonists to stimulate the secretion of both insulin and glucagon-like peptide-1 (GLP-1)...
July 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28285800/perspectives-on-cardiovascular-effects-of-incretin-based-drugs-from-bedside-to-bench-return-trip
#10
Michaela Luconi, Giulia Cantini, Antonio Ceriello, Edoardo Mannucci
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood...
March 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28270438/menin-and-prmt5-suppress-glp1-receptor-transcript-and-pka-mediated-phosphorylation-of-foxo1-and-creb
#11
Abdul Bari Muhammad, Bowen Xing, Chengyang Liu, Ali Naji, Xiaosong Ma, Rebecca A Simmons, Xianxin Hua
Menin is a scaffold protein that interacts with several epigenetic mediators to regulate gene transcription, and suppresses pancreatic β-cell proliferation. Tamoxifen-inducible deletion of multiple endocrine neoplasia type 1 (MEN1) gene, which encodes the protein menin, increases β-cell mass in multiple murine models of diabetes and ameliorates diabetes. Glucagon-like-peptide-1 (GLP1) is another key physiological modulator of β-cell mass and glucose homeostasis. However, it is not clearly understood whether menin crosstalks with GLP1 signaling...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28244632/safety-issues-with-glucagon-like-peptide-1-receptor-agonists-pancreatitis-pancreatic-cancer-and-cholelithiasis-data-from-randomized-controlled-trials
#12
Matteo Monami, Besmir Nreu, Alessia Scatena, Barbara Cresci, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
AIM: Glucagon-like peptide 1 receptor agonists (GLP1-RA) have been associated with an increased risk of pancreatitis and pancreatic cancer. Prior meta-analyses of randomized controlled trials failed to show any significant increase of risk; however, those meta-analyses did not include the recently published cardiovascular outcome trials (CVOT) with GLP1-RA, which provide a substantial additional body of data. The aim of the present meta-analysis is to assess the effect of GLP1-RA on pancreatitis, pancreatic cancers and cholelithiasis...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#13
Willem van den Brink, Annette Emerenciana, Francesco Bellanti, Oscar Della Pasqua, Jan Willem van der Laan
Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products...
April 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#14
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164753/evaluation-of-the-influence-of-the-conjugation-site-of-the-chelator-agent-hynic-to-glp1-antagonist-radiotracer-for-insulinoma-diagnosis
#15
Bluma Linkowski Faintuch, Daniele Seo, Érica Aparecida De Oliveira, Roselaine Campos Targino, Ana Maria Moro
Radiotracer diagnosis of insulinoma, can be done using somatostatin or glucagon-like peptide 1 (GLP-1). Performance of GLP-1 antagonists tends to be better than of agonists. We investigated the uptake of the antagonist exendin (9-39), radiolabeled with technetium-99m. Two different sites of the biomolecule were selected for chelator attachment. HYNIC-βAla chelator attached to serine (C- terminus) of exendin, was associated with higher tumor uptake than to aspartate (N- terminus). In conclusion the chelator position in the biomolecule influenced receptor uptake...
January 26, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/28105738/glucagon-like-peptide-1-receptor-agonists-and-risk-of-acute-pancreatitis-in-patients-with-type-2-diabetes
#16
Heidi Storgaard, Frederik Cold, Lise L Gluud, Tina Vilsbøll, Filip K Knop
Glucagon-like peptide-1 receptor agonist (GLP-1RAs) labels warn about acute pancreatitis (AP) and impose upon doctors the obligation to inform patients about symptoms of AP. Here we systematically reviewed the risk of AP in randomized placebo-controlled trials (RCTs) investigating the effect of GLP-1RAs in type 2 diabetes. We performed a systematic review with meta-analysis of long-term (minimum 24 months), placebo-controlled GLP-1RA RCTs in which AP was a predefined adverse event and adjudicated by blinded and independent adjudicating committees...
June 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28077257/real-world-effectiveness-and-safety-of-dapagliflozin-therapy-added-to-a-glp1-receptor-agonist-in-patients-with-type-2-diabetes
#17
J J Gorgojo-Martínez, C Serrano-Moreno, A Sanz-Velasco, G Feo-Ortega, F Almodóvar-Ruiz
BACKGROUND AND AIM: To evaluate the effectiveness and safety of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, dapagliflozin, in patients with type 2 diabetes mellitus (T2DM) and background glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy. METHODS AND RESULTS: This is a 12-month, real-world observational study, which assessed the effectiveness and safety of dapagliflozin in patients with T2DM and background GLP1-RA therapy. The main outcome measures were changes in A1C and weight at 6 and 12 months from baseline...
February 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27903028/-cardiovascular-morbidity-and-mortality-in-patients-with-kidney-disease
#18
REVIEW
Ivo Quack, Ralf Westenfeld
Patients with kidney disease have a significantly increased cardiovascular morbidity and mortality. Especially diabetics have an increased risk to develop renal insufficiency and cardiovascular events. Two recent studies show that the SGLT2 inhibitor Empagliflozin and the GLP1 agonist Liraglutid are able to lower the cardiovascular risk of type2 diabetics with renal insufficiency. Recent observations suggest that bradycardia and asystole are main triggers for sudden cardiac death in patients with chronic kidney disease...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27872157/exendin-4-increases-oxygen-consumption-and-thermogenic-gene-expression-in-muscle-cells
#19
Jin-Seung Choung, Young-Sun Lee, Hee-Sook Jun
Glucagon-like peptide-1 (GLP1) has many anti-diabetic actions and also increases energy expenditure in vivo As skeletal muscle is a major organ controlling energy metabolism, we investigated whether GLP1 can affect energy metabolism in muscle. We found that treatment of differentiated C2C12 cells with exendin-4 (Ex-4), a GLP1 receptor agonist, reduced oleate:palmitate-induced lipid accumulation and triglyceride content compared with cells without Ex-4 treatment. When we examined the oxygen consumption rate (OCR), not only the basal OCR but also the OCR induced by oleate:palmitate addition was significantly increased in Ex-4-treated differentiated C2C12 cells, and this was inhibited by exendin-9, a GLP1 receptor antagonist...
February 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27780892/diabetes-negatively-affects-cortical-and-striatal-gabaergic-neurons-an-effect-that-is-partially-counteracted-by-exendin-4
#20
Martin Larsson, Grazyna Lietzau, David Nathanson, Claes-Göran Östenson, Carina Mallard, Maria E Johansson, Thomas Nyström, Cesare Patrone, Vladimer Darsalia
Type 2 diabetic (T2D) patients often develop early cognitive and sensorimotor impairments. The pathophysiological mechanisms behind these problems are largely unknown. Recent studies demonstrate that dysfunctional γ-aminobutyric acid (GABAergic) neurons are involved in age-related cognitive decline. We hypothesized that similar, but earlier dysfunction is taking place under T2D in the neocortex and striatum (two brain areas important for cognition and sensorimotor functions). We also hypothesized that the T2D-induced effects are pharmacologically reversible by anti-diabetic drugs targeting the glucagon-like peptide-1 receptor (GLP-1R)...
December 2016: Bioscience Reports
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