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glp-1 agonist

Carol H Wysham, Dominic Pilon, Mike Ingham, Marie-Hélène Lafeuille, Bruno Emond, Rhiannon Kamstra, Michael Pfeifer, Patrick Lefebvre
OBJECTIVE: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting. METHODS: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012-April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics...
March 2018: Endocrine Practice
Xuan Du, Wen Lu, Zijun Lu, Xinyu Shao, Chunhong Hu, Bimin Shi
Background: To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods: 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups...
2018: Journal of Diabetes Research
Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
Adrian H Heald, Mark Livingston, Zuzanna Bien, Gabriela Y C Moreno, Ian Laing, Mike Stedman
BACKGROUND: In the financial year 2016/17 there were 52.0 million items prescribed for diabetes at a total net ingredient cost of £983.7 million - up from 28.9 million prescription items and £572.4 million in 2006/07. Anti-diabetes drugs (British National Formulary section 6.1.2) make up 45.1 per cent of the total £983.7 million net ingredient cost of drugs used in diabetes and account for 72.0 per cent of prescription items for all diabetes prescribing. METHODS: We examined the way that agents licensed to treat type 2 diabetes were used across GP practices in England in the year 2016/2017...
March 14, 2018: International Journal of Clinical Practice
Olga Montvida, Jonathan Shaw, Lawrence Blonde, Sanjoy K Paul
AIMS: To inform patients and their carers about the probability of reducing HbA1c to clinically desirable levels and sustainability of such control over 2 years with major second-line anti-diabetic therapies under individual risk scenario, with and without third-line intensification. MATERIALS AND METHODS: From US Centricity Electronic Medical Records, 163,081 patients with type 2 diabetes aged 18-80 years, who initiated metformin; intensified with DPP-4 inhibitor (DPP-4i), GLP-1 receptor agonist (GLP-1RA), sulfonylurea, insulin, or thiazolidinedione; and continued second-line ≥ 6 month, were selected...
March 14, 2018: Diabetes, Obesity & Metabolism
Tom Podewin, Julia Ast, Johannes Broichhagen, Nicholas H F Fine, Daniela Nasteska, Philipp Leippe, Manuel Gailer, Teresa Buenaventura, Nisha Kanda, Ben J Jones, Celine M'Kadmi, Jean-Louis Baneres, Jacky Marie, Alejandra Tomas, Dirk Trauner, Anja Hoffmann-Röder, David J Hodson
Understanding the activation and internalization of G protein-coupled receptors (GPCRs) using conditional approaches is paramount to developing new therapeutic strategies. Here, we describe the design, synthesis, and testing of ExONatide , a benzylguanine-linked peptide agonist of the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR required for maintenance of glucose levels in humans. ExONatide covalently binds to SNAP-tagged GLP-1R-expressing cells, leading to prolonged cAMP generation, Ca2+ rises, and intracellular retention of the receptor...
February 28, 2018: ACS Central Science
Linxi Wang, Zhiqing Liu, Zhou Chen, Caihua Huang, Xiaohong Liu, Can Chen, Xiaoyin Liu, Jingze Huang, Libin Liu, Donghai Lin
Although previous studies have reported the protective effect of glucagon-like peptide-1 (GLP-1) in diabetes nephropathy, the molecular mechanism such as nephroprotection remains elusive. In this study, we explored the molecular mechanism of exendin-4 as an GLP-1 receptor agonist for the treatment of tert-butyl hydroperoxide (t-BHP)-induced injury in mouse glomerulus mesangial cells (SV40 MES 13 cells) via an NMR-based metabonomic analysis. We found that exendin-4 protected mesangial cells from t-BHP-mediated toxicity, decreased the percentage of t-BHP-treated cells undergoing apoptosis, and restored glucose consumption in the t-BHP-treated group...
March 12, 2018: Free Radical Research
Marco Orsini Federici, Janette McQuillan, Giovanni Biricolti, Serena Losi, Jeremie Lebrec, Catrina Richards, Cristiana Miglio, Kirsi Norrbacka
INTRODUCTION: Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. METHODS: Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data)...
March 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
T Kimura, A Obata, M Shimoda, H Hirukawa, Y Kanda-Kimura, Y Nogami, K Kohara, S Nakanishi, T Mune, K Kaku, H Kaneto
AIMS: It is well-known that chronic exposure to large amounts of ligand leads to downregulation of its receptor. It is not known, however, whether a GLP-1R agonist downregulates its receptor. For this reason, our study examined whether GLP-1R expression is reduced after long-term exposure to dulaglutide (Dula) in non-diabetic and diabetic mice. METHODS: Seven-week-old male db/db and db/m mice were given either Dula (0.6mg/kg×2/week) or a control vehicle (CTL) for 17 weeks...
February 6, 2018: Diabetes & Metabolism
Katerina Kapodistria, Effie-Photini Tsilibary, Eleni Kotsopoulou, Petros Moustardas, Paraskevi Kitsiou
Liraglutide, a human long-lasting GLP-1 analogue, is currently regarded as a powerful treatment option for type 2 diabetes. Apart from glucoregulatory and insulinotropic actions, liraglutide increases β-cell mass through stimulation of β-cell proliferation and islet neogenesis, as well as inhibition of β-cell apoptosis. However, the underline molecular mechanisms have not been fully characterized. In this study, we investigated the mechanism by which liraglutide preserves islet β-cells in an animal model of overt diabetes, the obese db/db mice, and protects a mouse pancreatic β-cell line (βTC-6 cells) against apoptosis...
March 10, 2018: Journal of Cellular and Molecular Medicine
Banjun Ruan, Zheng Zhu, Zhao Yan, Wei Yang, Dongsheng Zhai, Li Wang, Zichen Ye, Huanyu Lu, An Xiang, Jingwei Liang, Yinghao Jiang, Chengming Xu, Zhenyu Wang, Ming Wei, Xiaoying Lei, Xiaorui Cao, Zifan Lu
BACKGROUND: The reciprocal fate decision of mesenchymal stem cells (MSCs) to either bone or adipocytes is determined by Wnt-related signaling and the glucagon-like peptide-1 receptor (GLP-1R). Azoramide, an ER stress alleviator, was reported to have an antidiabetic effect. In this study, we investigated the function of azoramide in regulating the lineage determination of MSCs for either adipogenic or osteogenic differentiation. METHODS: In this study, microcomputed tomography and histological analysis on bone morphogenetic protein (BMP)2-induced parietal periosteum bone formation assays, C3H10T1/2 and mouse bone marrow MSC-derived bone formation and adipogenesis assays, and specific staining for bone tissue and lipid droplets were used to evaluate the role of azoramide on the lineage determination of MSC differentiation...
March 9, 2018: Stem Cell Research & Therapy
Ian Blumer, Jeremy H Pettus, Tricia Santos Cavaiola
Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone...
March 9, 2018: Postgraduate Medicine
Petar M Seferović, Mark C Petrie, Gerasimos S Filippatos, Stefan D Anker, Giuseppe Rosano, Johann Bauersachs, Walter J Paulus, Michel Komajda, Francesco Cosentino, Rudolf A de Boer, Dimitrios Farmakis, Wolfram Doehner, Ekaterini Lambrinou, Yuri Lopatin, Massimo F Piepoli, Michael J Theodorakis, Henrik Wiggers, John Lekakis, Alexandre Mebazaa, Mamas A Mamas, Carsten Tschöpe, Arno W Hoes, Jelena P Seferović, Jennifer Logue, Theresa McDonagh, Jillian P Riley, Ivan Milinković, Marija Polovina, Dirk J van Veldhuisen, Mitja Lainscak, Aldo P Maggioni, Frank Ruschitzka, John J V McMurray
The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice...
March 8, 2018: European Journal of Heart Failure
Gian Paolo Fadini, Giancarlo Zatti, Ileana Baldi, Daniele Bottigliengo, Agostino Consoli, Andrea Giaccari, Giorgio Sesti, Angelo Avogaro
In randomized controlled trials (RCTs), SGLT-2 inhibitors (SGLT2i) showed glycaemic and extra-glycaemic benefits. The DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes) was a multicenter retrospective study designed to evaluate baseline characteristics of patients receiving dapagliflozin versus selected comparators (DPP-4 inhibitors, gliclazide, or GLP-1 receptor agonists), and drug effectiveness in routine clinical practice. From a population of 281,217 patients, the analysis included 17,285 initiating dapagliflozin or comparator glucose lowering medications (GLM), 6751 of whom had a follow-up examination...
March 8, 2018: Diabetes, Obesity & Metabolism
Xiaoying He, Hongyu Guan, Weiwei Liang, Zhimin Huang, Lijuan Xu, Pengyuan Zhang, Fen Xu, Yanbing Li
BACKGROUND: Abdominal obesity is considered a major factor in the development of metabolic disorders. Glucagon-like peptide-1 (GLP-1) has been reported to have positive effects on improving body metabolism and to reducing insulin resistance. However, it remains less clear whether GLP-1 plays a role in the adipogenesis process of visceral fat. METHODS: Here, we analyzed the in vitro actions and probable mechanisms of Exendin-4, a GLP-1 receptor agonist, on human adipose-derived stromal cells (hADSCs) isolated from omentum...
February 8, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Jeong-Hwa Yoon, Se Hee Min, Chang Ho Ahn, Young Min Cho, Seokyung Hahn
We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and through April 2016. Bayesian network meta-analyses were performed with covariate adjustment...
March 6, 2018: Scientific Reports
Bahendeka Silver, Kaushik Ramaiya, Swai Babu Andrew, Otieno Fredrick, Sarita Bajaj, Sanjay Kalra, Bavuma M Charlotte, Karigire Claudine, Anthony Makhoba
A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A). Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A). Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin...
March 5, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Hua V Lin, Jingru Wang, Jie Wang, Weiji Li, Xuesong Wang, James T Alston, Melissa K Thomas, Daniel A Briere, Samreen K Syed, Alexander M Efanov
OBJECTIVE: GPR142 agonists are being pursued as novel diabetes therapies by virtue of their insulin secretagogue effects. But it is undetermined whether GPR142's functions in pancreatic islets are limited to regulating insulin secretion. The current study expands research on its action. METHODS AND RESULTS: We demonstrated by in situ hybridization and immunostaining that GPR142 is expressed not only in β cells but also in a subset of α cells. Stimulation of GPR142 by a selective agonist increased glucagon secretion in both human and mouse islets...
February 23, 2018: Molecular Metabolism
Gitanjali Srivastava, Caroline Apovian
PURPOSE OF REVIEW: Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity...
March 5, 2018: Current Obesity Reports
Nicole S Hernandez, Kelsey Y Ige, Elizabeth G Mietlicki-Baase, Gian Carlo Molina-Castro, Christopher A Turner, Matthew R Hayes, Heath D Schmidt
Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of the GLP-1 receptor agonist exendin-4 dose dependently reduced cocaine seeking in rats at doses that did not affect ad libitum food intake, meal patterns or body weight. We also demonstrated that systemic exendin-4 penetrated the brain where it putatively bound receptors on both neurons and astrocytes in the ventral tegmental area (VTA)...
February 14, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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