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Glp 1 agonist

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https://www.readbyqxmd.com/read/28817231/effect-of-once-weekly-dulaglutide-on-hba1c-and-fasting-blood-glucose-in-patient-subpopulations-by-gender-duration-of-diabetes-and-baseline-hba1c
#1
Baptist Gallwitz, Samuel Dagogo-Jack, Vivian Thieu, Luis-Emilio Garcia-Perez, Imre Pavo, Maria Yu, Kenneth E Robertson, Nan Zhang, Francesco Giorgino
To evaluate the efficacy and safety of dulaglutide 1.5 mg and 0.75 mg in type 2 diabetes patients by subgroups of gender, duration of diabetes, and baseline HbA1c in the dulaglutide clinical development program (AWARD-1 to -6 and -8 clinical trials). MATERIALS AND METHODS: Change in HbA1c was analysed by gender, duration of diabetes (<5 years, ≥5 years and <10 years, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia, and gastrointestinal adverse events were evaluated for individual trials...
August 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28816532/comparing-clinical-outcomes-and-costs-for-different-treatment-intensification-approaches-in-patients-with-type-2-diabetes-uncontrolled-on-basal-insulin-adding-glucagon-like-peptide-1-receptor-agonists-vs-adding-rapid-acting-insulin-or-increasing-basal-insulin
#2
Philip Levin, Tao Fan, Xue Song, Damion Nero, Brian Davis, Bong-Chul Chu
Objective-Not all patients with type 2 diabetes achieve the recommended glycated hemoglobin A1c (A1C) levels after adequate titration of basal insulin (BI). Current intensification approaches include addition of rapid-acting insulin (RAI) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA), but it is not clear which strategy results in better long-term outcomes. Methods-This retrospective analysis of health insurance claims data in the US MarketScan database compared glycemic control and healthcare resource utilization and costs 12 months after adding GLP-1 RA to BI vs adding RAI or increasing BI doses...
August 17, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28811669/paraventricular-thalamic-control-of-food-intake-and-reward-role-of-glucagon-like-peptide-1-receptor-signaling
#3
Zhi Yi Ong, Jing-Jing Liu, Zhiping P Pang, Harvey J Grill
Paraventricular thalamic nucleus (PVT) neurons receive hindbrain and hypothalamic inputs, and project to forebrain sites involved in reward and motivation function. The role of PVT in energy balance and reward control is however understudied. Given that PVT neurons express glucagon-like peptide-1 receptors (GLP-1R), which are critical to feeding and body weight control, we tested the hypothesis that PVT GLP-1R signaling contributes to food intake and reward inhibition. To assess the hypothesis, behavioral tests including chow and high-fat diet intake, meal patterns, conditioned place preference for high-fat food, cue-induced reinstatement of sucrose-seeking, and motivation to work for sucrose were employed following intra-PVT delivery of either GLP-1R agonist, exendin-4 (Ex4), or GLP-1R antagonist, exendin-9-39 (Ex9)...
July 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28811293/the-glucagon-like-peptide-1-receptor-in-the-ventromedial-hypothalamus-reduces-short-term-food-intake-in-male-mice-by-regulating-nutrient-sensor-activity
#4
Melissa A Burmeister, Jacob D Brown, Jennifer E Ayala, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the glucagon-like peptide 1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent upon AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR). We found that pharmacological inhibition of glycolysis and, thus, activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28807775/the-potential-benefits-of-glucagon-like-peptide-1-receptor-agonists-for-diabetic-retinopathy
#5
REVIEW
Baoying Pang, Huanran Zhou, Hongyu Kuang
For a long time, diabetic retinopathy (DR) has been one of the most severe complications of diabetes. The early treatment of DR is not clearly recognized. The additional benefit of hypoglycemic agents for DR has become a new research field. Glucagon-like peptide-1 receptor (GLP-1R) has been shown to be widely expressed in tissues including retina. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been generally used in the treatment of diabetic patients. Studies shows that GLP-1RA could inhibit nerve damage by decrease apoptosis of nerve cells and activation of glial cells...
August 11, 2017: Peptides
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
#6
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/28800417/buccal-delivery-of-small-molecules-and-biologics-of-mucoadhesive-polymers-films-and-nanoparticles
#7
REVIEW
Javier O Morales, David J Brayden
Buccal delivery of macromolecules (biologics) sets a great challenge for researchers. Although several niche small molecule products have been approved as simple sprays, tablets and oral films, it is not simply a case of adapting existing technologies to biologics. Buccal delivery of insulin has reached clinical trials with two approaches: oromucosal sprays of the peptide with permeation enhancers, and embedded gold nanoparticles in a dissolvable film. However, neither of these approaches have led to FDA approvals likely due to poor efficacy, submaximal peptide loading in the dosage form, and to wide intra-subject variability in pharmacokinetics and pharmacodynamics...
August 8, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28799414/the-clinical-use-of-a-fixed-dose-combination-of-insulin-degludec-and-liraglutide-xultophy-100-3-6-for-the-treatment-of-type-2-diabetes
#8
Kira Harris, Kimberly Lovin Nealy
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of the fixed-dose combination of insulin degludec and the glucagon-like peptide-I receptor agonist (GLP-1 RA), liraglutide (IDegLira) in the treatment of type 2 diabetes mellitus (T2DM). DATA SOURCES: A PubMed and MEDLINE search (1966 to July 2017) of the keywords insulin degludec, liraglutide, and type 2 diabetes mellitus was conducted. References were reviewed to identify additional citations...
August 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#9
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/28792489/l-phenylalanine-modulates-gut-hormone-release-and-glucose-tolerance-and-suppresses-food-intake-through-the-calcium-sensing-receptor-in-rodents
#10
A Alamshah, E Spreckley, M Norton, J S Kinsey-Jones, A Amin, A Ramgulam, Y Cao, R Johnson, K Saleh, E Akalestou, Z Malik, N Gonzalez-Abuin, A Jomard, R Amarsi, A Moolla, P R Sargent, G W Gray, S R Bloom, K G Murphy
OBJECTIVE: High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. METHODS: We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo...
July 13, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28781108/exenatide-once-weekly-versus-placebo-in-parkinson-s-disease-a-randomised-double-blind-placebo-controlled-trial
#11
Dilan Athauda, Kate Maclagan, Simon S Skene, Martha Bajwa-Joseph, Dawn Letchford, Kashfia Chowdhury, Steve Hibbert, Natalia Budnik, Luca Zampedri, John Dickson, Yazhou Li, Iciar Aviles-Olmos, Thomas T Warner, Patricia Limousin, Andrew J Lees, Nigel H Greig, Susan Tebbs, Thomas Foltynie
BACKGROUND: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period...
August 3, 2017: Lancet
https://www.readbyqxmd.com/read/28772236/a-novel-glucagon-like-peptide-1-glucagon-receptor-dual-agonist-exhibits-weight-lowering-and-diabetes-protective-effects
#12
Jie Zhou, Xingguang Cai, Xun Huang, Yuxuan Dai, Lidan Sun, Bo Zhang, Bo Yang, Haiyan Lin, Wenlong Huang, Hai Qian
Glucagon has plenty of effects via a specific glucagon receptor(GCGR) like elevating the blood glucose, improving fatty acids metabolism, energy expenditure and increasing lipolysis in adipose tissue. The most important role of glucagon is to regulate the blood glucose, but the emergent possibilities of hyperglycaemia is exist. Glucagon could also slightly activate glucagon-like peptide-1 receptor(GLP-1R), which lead to blood glucose lowering effect. This study aims to erase the likelihood of hyperglycaemia and to remain the inherent catabolic effects through improving GLP-1R activation and deteriorating GCGR activation so as to lower the bodyweight and show diabetes-protective effects...
July 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28768173/the-sustained-effects-of-a-dual-gip-glp-1-receptor-agonist-nnc0090-2746-in-patients-with-type-2-diabetes
#13
Juan Pablo Frias, Edward J Bastyr, Louis Vignati, Matthias H Tschöp, Christophe Schmitt, Klara Owen, Rune Haubo Christensen, Richard D DiMarchi
Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28763894/-cardiovascular-benefits-and-underlying-mechanisms-of-glp-1-receptor-agonists-in-patients-with-type-2-diabetes
#14
J Ke, J J Zhang, T P Hong
No abstract text is available yet for this article.
July 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28761216/use-of-canagliflozin-in-combination-with-and-compared-to-incretin-based-therapies-in-type-2-diabetes
#15
Richard E Pratley, Eugenio Cersosimo
In Brief Sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies (dipeptidyl peptidase-4 [DPP-4] inhibitors and glucagon-like peptide-1 [GLP-1] receptor agonists) are widely used to treat patients with type 2 diabetes. In clinical and real-world studies, canagliflozin, an SGLT2 inhibitor, has demonstrated superior A1C lowering compared to the DPP-4 inhibitor sitagliptin. Canagliflozin can also promote modest weight/fat loss and blood pressure reduction. The addition of canagliflozin to treatment regimens that include a DPP-4 inhibitor or a GLP-1 receptor agonist has been shown to further improve glycemic control, while still maintaining beneficial effects on cardiometabolic parameters such as body weight and blood pressure...
July 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/28761132/exendin-4-reduces-food-intake-via-the-pi3k-akt-signaling-pathway-in-the-hypothalamus
#16
Yan Yang, Pique P Choi, Wanli W Smith, Weijie Xu, Delin Ma, Zachary A Cordner, Nu-Chu Liang, Timothy H Moran
Exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus. In this study, we examined the potential neural mechanisms by which these effects occur. Male Sprague Dawley rats were implanted with a cannula in the third ventricle of the brain through which an inhibitor of phosphatidylinositol-3 kinase (PI3K) (wortmannin) was administered, and EX-4 or vehicle was administered via intraperitoneal (IP) injection...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760227/relevance-of-weight-in-the-management-of-patients-with-type-2-diabetes-mellitus-towards-an-adipocentric-approach-to-diabetes
#17
Juan José Gorgojo Martínez
In recent decades, there has been a worldwide parallel increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), which is not surprising, given that increased visceral fat is the main risk factor for the development of T2DM in genetically predisposed individuals. An intervention focused on intensive blood glucose control in T2DM with classic drugs increases the risk of weight gain and the rate of hypoglycaemia. In contrast, weight loss through lifestyle changes, drugs and/or surgery simultaneously improves most cardiovascular (CV) risk factors, including hyperglycemia...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28757640/effects-of-peripheral-administration-of-a-neuromedin-u-receptor-2-selective-agonist-on-food-intake-and-body-weight-in-obese-mice
#18
T Kaisho, H Nagai, T Asakawa, N Suzuki, H Fujita, K Matsumiya, N Nishizawa, Y Kanematsu-Yamaki, K Dote, J-I Sakamoto, T Asami, S Takekawa
BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions including regulation of smooth-muscle contraction, blood pressure, stress responses, and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system, respectively. It is reported that the NMU signaling system regulates food intake and body weight via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity...
July 31, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28756460/ursolic-acid-activates-the-tgr5-receptor-to-enhance-glp-1-secretion-in-type-1-like-diabetic-rats
#19
Shih-Hsiang Lo, Yingxiao Li, Kai Chun Cheng, Chiang-Shan Niu, Juei-Tang Cheng, Ho-Shan Niu
Endogenous Takeda G-protein-coupled receptor 5 (TGR5), G-protein-coupled bile acid receptor 1 (GPBAR1), regulates glucose metabolism. In animals, TGR5 activation by a chemical agonist may increase incretin secretion and reduce the blood sugar level. Recently, betulinic acid has been suggested to activate TGR5. Ursolic acid is a well-known pentacyclic triterpenoid that is similar to betulinic acid. It is of special interest to determine the potential effect of ursolic acid on TGR5. Therefore, we transfected cultured Chinese hamster ovary (CHO-K1) cells with the TGR5 gene...
July 30, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28754350/beneficial-metabolic-effects-of-dietary-epigallocatechin-gallate-alone-and-in-combination-with-exendin-4-in-high-fat-diabetic-mice
#20
Nupur M Pathak, Paul J B Millar, Varun Pathak, Peter R Flatt, Victor A Gault
OBJECTIVE: Significant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity. METHODS: EGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin...
July 25, 2017: Molecular and Cellular Endocrinology
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