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exenatide non diabetic

Judy W M Cheng, Hisham A Badreldin, Dhiren K Patel, Snehal H Bhatt
This article reviews evidence of benefits and risk of antidiabetic agents in cardiovascular (CV) outcomes, with a focus on medications approved by the FDA since 2008. Peer-reviewed articles were identified from MEDLINE and Current Content database (both 1966 to October 1, 2016) using the search terms insulin, metformin, rosiglitazone, pioglitazone, glyburide, glipizide, glimepiride, acarbose, miglitol, albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide, pramlintide, meglitinide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, colesevalam, bromocriptine, mortality, myocardial infarction (MI), heart failure, (HF) and stroke...
January 18, 2017: Current Medical Research and Opinion
Kun Ho Yoon, Elise Hardy, Jenny Han
BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations. METHODS: We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7...
December 26, 2016: Diabetes & Metabolism Journal
Stefania Camastra, Brenno Astiarraga, Andrea Tura, Silvia Frascerra, Demetrio Ciociaro, Andrea Mari, Amalia Gastaldelli, Ele Ferrannini
AIMS: To investigate the effect of exenatide on glucose disposal, insulin secretion, ß-cell function, lipolysis, and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions. MATERIALS AND METHODS: Patients were assigned to exenatide 10 µg twice daily (EXE, n = 15) or control (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measure endogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretion rate (ISR), ß-cell function, hepatic (HIR) and adipose tissue insulin resistance (AT-IR) and insulin sensitivity (IS)...
November 29, 2016: Diabetes, Obesity & Metabolism
Pelle L Ishøy, Filip K Knop, Brian V Broberg, Nikolaj Bak, Ulrik B Andersen, Niklas R Jørgensen, Jens J Holst, Birte Y Glenthøj, Bjørn H Ebdrup
AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects such as obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia...
February 2017: Diabetes, Obesity & Metabolism
Zhiqiang Li, Lihua Huang, Xiao Yu, Can Yu, Hongwei Zhu, Xia Li, Duo Han, Hui Huang
OBJECTIVES: The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. METHODS: Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days...
January 2017: Pancreas
John E Anderson, Vivian T Thieu, Kristina S Boye, Ryan T Hietpas, Luis-Emilio Garcia-Perez
Approximately 90% of T2D patients in the US are diagnosed and treated in the primary care setting, and the majority of the burden of disease management falls to primary care providers. Here, we discuss the clinical data for once weekly dulaglutide, e.g. the results of seven completed Phase 3 trials, patient preference studies, patient reported outcomes (PRO), and clinical data surrounding the dulaglutide administration device. Dulaglutide 1.5 mg once weekly demonstrated superiority to placebo, metformin, sitagliptin, exenatide BID, and insulin glargine (in 2 trials), and non-inferiority to liraglutide in reduction of HbA1c from baseline, with an acceptable safety profile...
November 2016: Postgraduate Medicine
Ngoc-Thanh Thi Nguyen, Jae Sun Lee, Soi Yun, E K Lee
Exenatide is a synthetic version of the 39-mer peptide of Exendin-4, which is an FDA-approved therapeutic against Type II diabetes mellitus. However, exenatide has a very short in-serum half-life and PEGylation have been performed to improve its in-serum stability. PEGylation often yields multivalent binding to non-specific residues, and the desired species should be carefully separated by chromatographies. In this study, we first devised an aqueous-phase, two-step PEGylation process. This consists of thiolation of Lys 12 and 27 residues followed by attachment of PEG-maleimide (10kD) to thiol groups...
July 29, 2016: Journal of Chromatography. A
Na Su, Yun Li, Ting Xu, Ling Li, Joey Sum-Wing Kwong, Heyue Du, Kaiun Ren, Qianrui Li, Jianshu Li, Xin Sun, Sheyu Li, Haoming Tian
BACKGROUND/OBJECTIVES: Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is increasingly used in obese or overweight patients with diabetes. However, its safety profile and effects on weight loss in non-diabetic obese or overweight population remain unclear. We aimed to evaluate efficacy and safety of exenatide in obese or overweight participants without diabetes. METHODS: We searched up to January 2016 in MEDLINE (Ovid SP), EMBASE (Ovid SP), Cochrane Central Register of Controlled Trials (CENTRAL), some Chinese databases and ClinicalTrials...
September 15, 2016: International Journal of Cardiology
A J Scheen
Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme demonstrated the efficacy and safety of dulaglutide in patients with type 2 diabetes treated by diet and exercise, metformin, a combination of metformin and a sulfonylurea or metformin and pioglitazone or even by supplements of prandial insulin. In the AWARD programme, dulaglutide (subcutaneous 0.75 or 1.5 mg once weekly) exerted a greater glucose-lowering activity than metformin, sitagliptin, exenatide or insulin glargine, and was non-inferior to liraglutide 1...
March 2016: Revue Médicale de Liège
Y Hu, J Liu, H Zhang, Y Xu, T Hong, G Wang
AIM: Fibroblast growth factor 21 (FGF21) has been demonstrated to be a metabolic regulator with beneficial effects. Several studies have shown that type 2 diabetes mellitus (T2DM) patients have increased FGF21 levels and decreased expression of FGF receptors, suggesting a state of 'FGF21 resistance'. The aim of this study was to investigate the effects of the glucagon-like peptide (GLP)-1 receptor agonist exenatide on FGF21 levels and other metabolic parameters in patients with newly diagnosed T2DM...
November 2016: Diabetes & Metabolism
Johan Jendle, George Grunberger, Thomas Blevins, Francesco Giorgino, Ryan T Hietpas, Fady T Botros
Dulaglutide (DU) is a once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for the treatment of type 2 diabetes mellitus (T2DM). Glycaemic efficacy and safety characteristics of DU have been assessed in six Phase 3 studies in the AWARD program. The objective of this review article is to summarise these results from the 6 completed AWARD studies. At the primary endpoint, in 5 of the 6 studies, once weekly dulaglutide 1.5 mg was superior to the active comparator (exenatide, insulin glargine [two studies], metformin, and sitagliptin), with a greater proportion of patients reaching glycated haemoglobin A1c (HbA1c) targets of <7...
April 21, 2016: Diabetes/metabolism Research and Reviews
P Salehi, I Hsu, C G Azen, S D Mittelman, M E Geffner, D Jeandron
BACKGROUND: Prader-Willi syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity because of obesity without effective medical treatment targeting hyperphagia. Exenatide (Byetta [synthetic Exendin-4]; AstraZeneca, Wilmington DE) is a GLP-1 receptor agonist which reduces appetite and weight and may be an effective treatment in PWS. OBJECTIVE: The objective of this study is to determine the effect of a 6-month trial of exenatide on appetite, weight and gut hormones in youth with PWS...
April 13, 2016: Pediatric Obesity
Eduardo García Díaz, Danila Guagnozzi, Verónica Gutiérrez, Carmen Mendoza, Cristina Maza, Yulene Larrañaga, Dolores Perdomo, Teresa Godoy, Ghalli Taleb
AIM: To compare the effect of different hypoglycemic drugs on laboratory and ultrasonographic markers of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes not controlled on metformin alone. METHODS: Prospective study of diabetic patients treated with metformin in combination with gliclazide, pioglitazone, sitagliptin, exenatide, or liraglutide. NAFLD was assessed by abdominal ultrasound and NAFLD fibrosis score was calculated at baseline and 6 months...
May 2016: Endocrinología y Nutrición: órgano de la Sociedad Española de Endocrinología y Nutrición
Savvoula Savvidou, Kyparissia Karatzidou, Kalliopi Tsakiri, Asterios Gagalis, Prodromos Hytiroglou, John Goulis
AIM: Diabetes mellitus type 2 (DMT2) and non-alcoholic fatty liver disease (NAFLD) are both characterized by decreased circulating adiponectin. Recently, glucagon-like peptide-1 receptor agonists have been shown to induce adiponectin's expression. However, their interaction on clinical grounds needs to be further elucidated. METHODS: DMT2 patients with abnormal aminotransferases were screened for NAFLD and subjected to liver biopsy (group A, n=17). A subgroup of patients (n=110), after assessed for eligibility criteria, was blindly randomized to receive either 6-month exenatide supplementation on glargine insulin (group B) or intense, self-regulated, insulin therapy alone (group C)...
March 2016: Diabetes Research and Clinical Practice
André J Scheen
Dulaglutide is a new once-weekly glucagon-like peptide-1 receptor agonist for the management of hyperglycemia in adult patients with type 2 diabetes. It stimulates dose-dependent insulin secretion and reduces glucagon secretion, both in a glucose-dependent manner. Efficacy on blood glucose control and safety were demonstrated in the large AWARD program in type 2 diabetic patients treated with diet, metformin, dual oral therapy or insulin lispro with or without metformin, confirming findings of pilot studies in Caucasian patients and data in Japanese patients...
2016: Expert Review of Clinical Pharmacology
Markus Wallner, Ewald Kolesnik, Klemens Ablasser, Mounir Khafaga, Paulina Wakula, Senka Ljubojevic, Eva Maria Thon-Gutschi, Harald Sourij, Martin Kapl, Nicholas J Edmunds, J Brent Kuzmiski, David A Griffith, Igor Knez, Burkert Pieske, Dirk von Lewinski
Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of drugs developed for treating type-2 diabetes mellitus. Patients with diabetes carry an up to 5-fold greater mortality risk compared to non-diabetic patients, mainly as a result of cardiovascular diseases. Although beneficial cardiovascular effects have been reported, exact mechanisms of GLP-1R-agonist action in the heart, especially in human myocardium, are poorly understood. The effects of GLP-1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac contractility were tested in non-failing atrial and ventricular trabeculae from 72 patients...
December 2015: Journal of Molecular and Cellular Cardiology
Undine E Lang, Christoph Beglinger, Nina Schweinfurth, Marc Walter, Stefan Borgwardt
Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota) acting in gut brain circuits...
2015: Cellular Physiology and Biochemistry
Hui Wu, Chunhua Sui, Fangzhen Xia, Hualing Zhai, Huixin Zhang, Hui Xu, Pan Weng, Yingli Lu
PURPOSE: The glucagon-like peptide (GLP)-1 agonist exenatide shows the same multiple effects on glucose homeostasis as native GLP-1, which can reduce blood glucose levels in individuals with type-2 diabetes mellitus (T2DM). However, its underlying action mechanism on glucose metabolism in the skeletal muscle of T2DM cases is unknown. We investigated the effects and action mechanisms of exenatide on insulin resistance (IR) in the skeletal muscle of high-fat diet and low-dose streptozotocin-induced T2DM rats...
2016: Endocrine Research
Tara Gurung, Deepson S Shyangdan, Joseph Paul O'Hare, Norman Waugh
BACKGROUND: Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. METHODS: MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015...
2015: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Wuquan Deng, Sheng Qiu, Gangyi Yang, Bing Chen
Glucagon-like peptide-1 (GLP-1) analogs, such as exenatide, have played an important role as antidiabetic medications in the treatment of type 2 diabetes (T2DM). Like most other hypoglycemic agents, exenatide has a number of actions, including lowering blood glucose, promoting weight loss, improving insulin resistance, and protecting islet β-cells. Although GLP-1 analogs, combined with other antidiabetic medications, have excellent performance in T2DM, some side effects and imperfections limit its use in clinical practice...
2015: Therapeutics and Clinical Risk Management
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