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https://www.readbyqxmd.com/read/28643293/-why-is-a-combination-of-basal-insulin-with-a-glp-1-receptor-agonist-useful-in-many-patients-with-type-2-diabetes
#1
Michael Nauck, Birgit Wilhelm
BACKGROUND: In 2015, the combination of basal insulin and GLP-1 receptor agonist (RA) was incorporated into the guideline recommendations for type 2 diabetes as an option for the last escalation step. The two antidiabetics to be injected subcutaneously are complementary regarding their respective main effects and limitations. Basal insulin is predominantly active between meals and in the fasting state, whereas the main action of GLP-1 RA consists in preventing an excessive postprandial blood glucose increase...
June 2017: MMW Fortschritte der Medizin
https://www.readbyqxmd.com/read/28639755/-the-combination-of-glp-1-analogs-and-sglt2-inhibitors-new-perspectives
#2
Claire Ritz, Jaafar Jaafar, Jacques Philippe
Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28637887/mitigating-cardiovascular-risk-in-type-2-diabetes-with-antidiabetes-drugs-a-review-of-principal-cardiovascular-outcome-results-of-empa-reg-outcome-leader-and-sustain-6-trials
#3
Sanjay Kaul
The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA)...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#4
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28625506/long-term-cost-effectiveness-of-two-glp-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus-in-the-italian-setting-liraglutide-versus-lixisenatide
#5
Barnaby Hunt, Nana Kragh, Ceilidh C McConnachie, William J Valentine, Maria C Rossi, Roberta Montagnoli
PURPOSE: Maintaining glycemic control is the key treatment target for patients with type 2 diabetes mellitus. In addition, the glucagon-like peptide-1 (GLP-1) receptor agonists may be associated with other favorable treatment characteristics, such as reduction in body weight and reduced risk of hypoglycemia compared with traditional diabetes interventions. The aim of the present analysis was to compare the long-term cost-effectiveness of 2 GLP-1 receptor agonists, liraglutide 1.8 mg and lixisenatide 20 μg (both administered once daily), in the treatment of patients with type 2 diabetes failing to achieve glycemic control with metformin monotherapy in the Italian setting...
June 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28624122/glucagon-like-peptide-1-and-insulin-synergistically-activate-vagal-afferent-neurons
#6
Yusaku Iwasaki, Chayon Goswami, Toshihiko Yada
Intestinal glucagon-like peptide-1 (GLP-1) and pancreatic insulin, released postprandially, commonly regulate glucose metabolism. Recent clinical experience indicates that the GLP-1R agonist and insulin in combination, compared to insulin alone, results in better glycemic and weight controls in type 2 diabetic patients. These observations suggest possible interactive effect of these hormones. These hormones, in addition to peripherally controlling glycemia, exert central regulation of food intake and glucose metabolism, the effect at least partly mediated by signaling to the brain via the vagal afferents...
May 25, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28616805/effects-of-insulin-plus-glucagon-like-peptide-1-receptor-agonists-glp-1ras-in-treating-type-1-diabetes-mellitus-a-systematic-review-and-meta-analysis
#7
REVIEW
Weihao Wang, Hongyan Liu, Shumin Xiao, Shuaihui Liu, Xin Li, Pei Yu
INTRODUCTION: Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) has already been proven an efficient treatment option for type 2 diabetes. This combination can effectively improve glycated hemoglobin levels, cause weight loss and reduce the dosage of insulin. In addition, it can also reduce the risk of hypoglycemia. Several randomized controlled trials have confirmed that this treatment may be just as effective for type 1 diabetes mellitus (T1DM) patients...
June 14, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28612625/glp-1-receptor-agonists-carotid-atherosclerosis-and-retinopathy
#8
Manfredi Rizzo, Dragana Nikolic, Francesco Di Pace, Nikolaos Papanas, Nicola Montano
No abstract text is available yet for this article.
June 21, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28612554/-the-preliminary-investigation-of-glp-1-receptor-agonist-on-liver-steatosis-in-obese-mice
#9
Xia Wang, He He, Li-Bo Liang, Mei Zhang, She-Yu Li, Shuang-Qing Li, Zhen-Mei An, Heng-Jian Huang
OBJECTIVES: To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, on liver function and steatosis in obese mice. METHODS: Male c57BL/6J mice (8 weeks old) were divided into high-fat-diet group (for obesity model construction) and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group [H group, intraperitoneal injection 0.02 μg/ (g·d) , high-fat-diet], low-dose exenatide group [L group, intraperitoneal injection 0...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28611211/metabolic-and-neuroprotective-effects-of-dapagliflozin-and-liraglutide-in-diabetic-mice
#10
Paul Millar, Nupur Pathak, Vadivel Parthsarathy, Tony Bjourson, Maurice O'Kane, Varun Pathak, R Charlotte Moffett, Peter R Flatt, Victor A Gault
This study assessed the metabolic and neuroprotective actions of the sodium glucose co-transporter-2 inhibitor dapagliflozin in combination with the GLP-1 agonist liraglutide in dietary-induced diabetic mice. Mice administered low-dose streptozotocin (STZ) on a high fat diet received dapagliflozin, liraglutide, dapagliflozin-plus-liraglutide (DAPA-Lira) or vehicle once-daily over 28 days. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, hormone and biochemical analysis, dual-energy x-ray absorptiometry densitometry, novel object recognition, islet and brain histology were examined...
June 13, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28609478/purification-of-family-b-g-protein-coupled-receptors-using-nanodiscs-application-to-human-glucagon-like-peptide-1-receptor
#11
Yingying Cai, Yuting Liu, Kelly J Culhane, Brian T DeVree, Yang Yang, Roger K Sunahara, Elsa C Y Yan
Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e...
2017: PloS One
https://www.readbyqxmd.com/read/28605180/a-hydrogel-microsphere-drug-delivery-system-that-supports-once-monthly-administration-of-a-glp-1-receptor-agonist
#12
Eric L Schneider, Brian R Hearn, Samuel J Pfaff, Ralph Reid, David G Parkes, Niels Vrang, Gary W Ashley, Daniel V Santi
We have developed a chemically-controlled very long-acting delivery system to support once-monthly administration of a peptidic GLP-1R agonist. Initially, the prototypical GLP-1R agonist exenatide was covalently attached to hydrogel microspheres by a self-cleaving β-eliminative linker; after subcutaneous injection in rats the peptide was slowly released into the systemic circulation. However, the short serum exenatide half-life suggested its degradation in the subcutaneous depot. We found that exenatide undergoes deamidation at Asn(28)with an in vitro and in vivo half-life of approximately two weeks...
June 12, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28605158/the-effect-of-liraglutide-on-dietary-lipid-induced-insulin-resistance-in-humans
#13
Juraj Koska, Lizette Lopez, Karen D'Souza, Tracy Osredkar, James Deer, Julie Kurtz, Arline D Salbe, S Mitchell Harman, Peter D Reaven
AIMS: High saturated fatty acid (SFA) diets blunt peripheral insulin action. GLP-1 receptor agonists suppress postprandial lipids and endothelial dysfunction, which may counter SFA-induced insulin resistance. This study tested whether liraglutide suppresses postprandial elevations in lipids and thus protects against high SFA-diet induced insulin resistance. MATERIALS AND METHODS: In a randomized placebo-controlled cross-over study, 32 subjects with normal or mildly impaired glucose tolerance received liraglutide and placebo for 3 weeks each...
June 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28598027/a-novel-gip-analog-zp4165-enhances-glp-1-induced-body-weight-loss-and-improves-glycemic-control-in-rodents
#14
P K Nørregaard, M A Deryabina, P Tofteng Shelton, J U Fog, J R Daugaard, P Eriksson, L F Larsen, L Jessen
AIM: To investigate the effects of the novel GIP analog, ZP4165, on body weight and glycemic control in rodents. Additionally, to investigate if ZP4165 modulates the anti-obesity and anti-hyperglycemic effects of a GLP-1 agonist (liraglutide). METHODS: The acute insulinotropic effect of ZP4165 was investigated in rats during an oral glucose tolerance test. Long-term effects of ZP4165 on body weight and glycemic control, either alone or in combination with liraglutide, were assessed in diet-induced obese mice and diabetic db/db mice...
June 9, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28596247/incretin-based-treatments-and-mortality-in-patients-with-type-2-diabetes-systematic-review-and-meta-analysis
#15
REVIEW
Jiali Liu, Ling Li, Ke Deng, Chang Xu, Jason W Busse, Per Olav Vandvik, Sheyu Li, Gordon H Guyatt, Xin Sun
Objective To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes.Design Systematic review and meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.Eligibility criteria Randomised controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors with placebo or active anti-diabetic drugs in patients with type 2 diabetes...
June 8, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28593550/yh18421-a-novel-gpr119-agonist-exerts-sustained-glucose-lowering-and-weight-loss-in-diabetic-mouse-model
#16
Yoo Hoi Park, Hyun Ho Choi, Dong Hoon Lee, Soo Yong Chung, Na Yeon Yang, Do Hoon Kim, Mi Kyeong Ju, Tae Dong Han, Su Youn Nam, Kyu-Won Kim
G-protein-coupled receptor 119 (GPR119) represents a promising target for the treatment of type 2 diabetes as it can increase both GLP-1 secretion from intestinal L cells and glucose-stimulated insulin secretion (GSIS) from pancreatic β cells. Due to this dual mechanism of action, the development of small molecule GPR119 agonists has received much interest for the treatment of type 2 diabetes. Here, we identified a novel small-molecule GPR119 agonist, YH18421 and evaluated its therapeutic potential. YH18421 specifically activated human GPR119 with high potency and potentiated GLP-1 secretion and GSIS in vitro cell based systems...
June 8, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28586439/ramp2-influences-glucagon-receptor-pharmacology-via-trafficking-and-signaling
#17
Jaimini Cegla, Ben J Jones, James V Gardiner, David J Hodson, Thomas Marjot, Emma R McGlone, Tricia M Tan, Stephen R Bloom
Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we have investigated the interaction of the GCGR with RAMP2, a member of the family of Receptor Activity Modifying Proteins.We have used a combination of competition binding experiments, cell surface ELISA, functional assays assessing the Gαs and Gq pathways and β-arrestin recruitment, and siRNA knockdown to examine the effect of RAMP2 on the GCGR...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28581209/the-effect-of-continuous-exenatide-infusion-on-cardiac-function-and-perioperative-glucose-control-in-cardiac-surgery-patients-a-single-blind-randomized-controlled-trial
#18
Michal Lipš, Miloš Mráz, Jana Kloučková, Petr Kopecký, Miloš Dobiáš, Jarmila Křížová, Jaroslav Lindner, Michaela Diamant, Martin Haluzík
To intensify perioperative glucose control while minimizing the risk of hypoglycemia and to evaluate the suggested cardioprotective effects of GLP-1-based treatments we performed a randomized controlled trial with the GLP-1 receptor agonist exenatide as add-on to standard perioperative insulin therapy in subjects undergoing elective cardiac surgery. 38 subjects with decreased left ventricular systolic function (ejection fraction ≤50%) scheduled for elective CABG (coronary artery by-pass grafting) were randomized to receive either exenatide or placebo in a continuous 72-hour i...
June 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28581207/improving-postprandial-hyperglycemia-in-patients-with-type-2-diabetes-already-on-basal-insulin-therapy-a-review-of-current-strategies
#19
REVIEW
Guillermo E Umpierrez, Timothy S Bailey, Danielle Carcia, Charles Shaefer, Jay H Shubrook, Neil Skolnik
A large number of patients with type 2 diabetes (T2D) on basal insulin do not reach their glycosylated hemoglobin A1c (HbA1c) goals and require additional therapy to address postprandial hyperglycemia. Guidelines from expert bodies have outlined several approaches to accomplish post-prandial glucose (PPG) control, and recent literature suggests several more. This article provides strategies for primary care physicians caring for patients with T2D who do not achieve glycemic control with basal insulin alone...
June 5, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28580281/glucagon-like-peptide-2-promotes-gallbladder-refilling-via-a-tgr5-independent-glp-2r-dependent-pathway
#20
Bernardo Yusta, Dianne Matthews, Grace B Flock, John R Ussher, Brigitte Lavoie, Gary M Mawe, Daniel J Drucker
OBJECTIVE: Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome. Unexpectedly, reports of gallbladder disease have been associated with the use of both GLP-1R and GLP-2R agonists and after bariatric surgery, although the mechanisms remain unknown...
June 2017: Molecular Metabolism
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