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Susan L Samson, Alan J Garber
Incretin-based therapies are important addition to our armamentarium for the treatment of type 2 diabetes (T2DM). There are six Glucagon-like peptide-1 receptor agonists (GLP-1RAs) which have received regulatory approval for clinical use. The short-acting GLP-1RAs include exenatide twice daily, liraglutide once daily, and lixisenatide once daily. The approved long-acting GLP-1RAs are administered weekly and are exenatide, albiglutide, and dulaglutide. Although all of these therapies lower hemoglobin A1C (HbA1C), there also are unique features of GLP-1RAs that have been made manifest from clinical trial data with regard to weight-loss efficacy, fasting and post-prandial glucose control, cardiovascular safety and protection, and gastrointestinal and injection adverse effects...
December 2016: Current Diabetes Reports
Kyung Hye Lee, Sang Jin Ha, Jong-Shin Woo, Gi-Ja Lee, So-Ra Lee, Jung Wook Kim, Hun Kuk Park, Weon Kim
BACKGROUND: Exenatide exerts cardioprotective effects by attenuating ischaemic reperfusion injury, possibly through activating the opening of mitochondrial ATP-sensitive potassium channels. We used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties in order to assess exenatide-mediated cardioprotection in IR injury. METHODS: We used an in vivo Sprague-Dawley rat IR model and ex vivo Langendorff injury model. In the left anterior descending artery (LAD) occlusion model, animals were randomly divided into three groups: sham-operated rats (Sham, n=5), IR-injured rats treated with placebo (IR, n=6), and IR-injured treated with exenatide (IR + EXE, n=6)...
September 23, 2016: Heart, Lung & Circulation
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 the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like 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...
September 26, 2016: Diabetes, Obesity & Metabolism
Sonal Singh, Eugene E Wright, Anita Ym Kwan, Juliette C Thompson, Iqra A Syed, Ellen E Korol, Nathalie A Waser, Maria B Yu, Rattan Juneja
AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched...
October 7, 2016: Diabetes, Obesity & Metabolism
Soo Lim, Gha Young Lee, Ho Seon Park, Dong-Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Young-Bum Kim, Hee-Sook Jun, Hak Chul Jang, Kyong Soo Park
AIMS: Enhancement of glucagon-like peptide-1 (GLP-1) reduces glucose levels and preserves pancreatic β-cell function, but its effect against restenosis is unknown. METHODS AND RESULTS: We investigated the effect of subcutaneous injection of exenatide or local delivery of a recombinant adenovirus expressing GLP-1 (rAd-GLP-1) into carotid artery, in reducing the occurrence of restenosis following balloon injury. As a control, we inserted β-galactosidase cDNA in the same vector (rAd-βGAL)...
October 4, 2016: Cardiovascular Research
James G Johnson, Jennifer N Langan, Chen Gilor
An 8-yr-old male golden lion tamarin ( Leontopithecus rosalia ) was diagnosed with diabetes mellitus based on hyperglycemia and persistent glycosuria. Initial treatment consisted of the oral antihyperglycemic medications glipizide and metformin that resulted in decreased blood glucose concentrations; however, marked glycosuria persisted. Insufficient improvement on oral antihyperglycemic therapy and poor feasibility of daily subcutaneous insulin therapy led to an investigation into an alternative therapy with extended-release exenatide, a glucagon-like peptide-1 (GLP-1) mimetic, at a dosage of 0...
September 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Omorogieva Ojo
OBJECTIVE: This review examines the use of exenatide twice daily in managing changes in markers of cardiovascular risk in patients with type 2 diabetes. BACKGROUND: Type 2 diabetes is a progressive metabolic disorder, which results from defects in insulin secretion and/or insulin action leading to chronic hyperglycaemia and associated cardiovascular complications. Despite the use of diet, exercise, oral antihyperglycaemic agents and insulin, the progressive nature of the condition means that the levels of the preventive and treatment measures would have to be increased and/or new therapies have to be developed in order to address the long term impact of type 2 diabetes...
2016: International Journal of Environmental Research and Public Health
Wei Tang, Qingxin Yuan, Bo Xu, Kwame Osei, Jie Wang
Proinsulin folding imperfections cause extensive beta-cell defects known in diabetes. Here, we investigated whether exenatide can alleviate such defects in proinsulin conversion, beta-cell survival, and insulin secretion, in the Ins2(+/Akita) beta-cells that have a spontaneous mutation (Cys 96 Tyr) in the insulin 2 gene caused dominant negative misfolding problem. 15 or 120 min exenatide administration substantially improves glucose-stimulated insulin secretion, marked in the secreted insulin levels and proinsulin/insulin ratio...
September 19, 2016: Molecular and Cellular Endocrinology
Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Fang Dong, Peter Öhman, Serge A Jabbour
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce glycaemia and weight, and improve cardiovascular risk factors via different mechanisms. We aimed to compare the efficacy and safety of co-initiation of the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled by metformin. METHODS: DURATION-8 was a 28 week, multicentre, double-blind, randomised, active-controlled phase 3 trial done at 109 sites in six countries...
September 15, 2016: Lancet Diabetes & Endocrinology
Brenda Cirincione, Donald E Mager
AIM: The aim of this analysis was to develop a core population pharmacokinetic system for the pharmacokinetic properties of immediate-release (IR) exenatide that can be used in subsequent analyses for novel sustained-release formulations. METHODS: Data from eight clinical trials evaluating a wide range of doses and different administration routes were available for analysis. All modelling and simulations were conducted using the nonlinear mixed-effect modelling program NONMEM...
September 21, 2016: British Journal of Clinical Pharmacology
Ehab Mudher Mikhael
Hypoglycemia is the most common side effects for most glucose-lowering therapies. It constitutes a serious risk that faces diabetic patients who fast during Ramadan (the 9th month in the Islamic calendar). New glucose-lowering classes like dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are efficacious in controlling blood glucose level with less tendency to induce hypoglycemia and thus may constitute a good choice for diabetic patients during Ramadan...
2016: Journal of Diabetes Research
Amalia Gastaldelli, Melania Gaggini, Giuseppe Daniele, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis Triplitt, Peter Fox, Nicolas Musi, Ralph DeFronzo, Patricia Iozzo
: GLP-1 receptor agonists (GLP-1-RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP-1-RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. 15 male subjects (age=56±8 y, BMI=29±1 kg/m(2) , A1c=5.7±0.1%) were studied on two occasions, with a double blind subcutaneous injection of exenatide (5 mcg) or placebo (PLC) 30 min before a 75-gram oral glucose tolerance test (OGTT)...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yu V Natochin, A S Marina, A V Kutina, E V Balbotkina, T A Karavashkina
We have found the physiological mechanism of intensification of the excessive fluid removal from the body under the action of glucagon-like peptide-1 and its analog exenatide. Under the water load in rats, exenatide significantly increased the clearance of lithium, reduced fluid reabsorption in the proximal tubule of the nephron and intensified reabsorption of sodium ions in the distal parts, which contributed to the formation of sodium-free water and faster recovery of osmotic homeostasis. Blocking this pathway with a selective antagonist of glucagon-like peptide-1 receptors slowed down the elimination of excessive water from the body...
July 2016: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
Qiang Ma, Jun-Jie Yang, Hao Zhou, Ying Zhang, Yun-Dai Chen
OBJECTIVE: To investigate the effect of exenatide on chemotactic migration of adipose-derived stem cells (ADSCs) and confirm that Rho GTPase is the downstream effector protein of SDF-1/CXCR-4 migration pathway. METHODS: ADSCs were isolated, cultured, identified by flow cytometry, and induced to differentiate in vitro. RTCA xCELLigence system was used to analyze the effect of exenatide on ADSC proliferation. The effects of exenatide at different concentrations, AMD3100 (CXCR-4 antagonist), and CCG-1423 (Rho GTPase antagonist) on chemotactic migration of ADSCs were tested using Transwell assay...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Aihua Zheng, Li Cao, Shu Qin, Yue Chen, Yong Li, Dongying Zhang
BACKGROUND: It is reported that glucagon-like peptide-1 (GLP-1) has direct cardioprotective effects. We hypothesise that Exenatide, a long half-life analog of GLP-1, might protect the heart against ischaemia/reperfusion (I/R) injury. In this study, the role and mechanism of Exenatide in I/R was investigated. METHODS: Two p38 MAPK isoforms, p38α or p38γ, were knocked down by recombinant adeno-associated virus (rAAV) in male Sprague-Dawley rats. Then, rats were randomly treated with Exenatide or PBS before I/R...
August 17, 2016: Heart, Lung & Circulation
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mark H H Kramer, Michaela Diamant, Erik H Serné, Daniël H van Raalte
OBJECTIVE: To assess the effects of glucagon-like peptide (GLP)-1-based therapies (ie, GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) on microvascular function in patients with type 2 diabetes mellitus. APPROACH AND RESULTS: We studied 57 patients with type 2 diabetes mellitus (mean±SD age: 62.8±6.9 years; body mass index: 31.8±4.1 kg/m(2); HbA1c [glycated hemoglobin] 7.3±0.6%) in an acute and 12-week randomized, placebo-controlled, double-blind trial conducted at the Diabetes Center of the VU University Medical Center...
October 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Puxiu Wang, Qian Wang, Tianyang Ren, Haoyu Gong, Jingxin Gou, Yu Zhang, Cuifang Cai, Xing Tang
Pluronic F127 and PEG as a multi-gel-core were used to prepare Exenatide-loaded microspheres and store the drug within the microspheres. Also, the sol-gel transition and novel functions of the Pluronic F127-PEG gel core were investigated.Microspheres with a multi-gel-core (GCMs) and without a multi-gel-core (Ms) were compared in terms of the rate of PLGA degradation, therelease kinetics in vitro and the efficacy in KKAy mice. The drug release of GCMs was at a constant rate, and slower than Ms. In addition, after the KKAy mice were given Exenatide for 55days, the blood glucose concentration and HbA1c concentration in the GCMs group were lower than that in the Ms group...
November 1, 2016: Colloids and Surfaces. B, Biointerfaces
Per Lundkvist, C David Sjöström, Sam Amini, Maria J Pereira, Eva Johnsson, Jan W Eriksson
AIMS: Dapagliflozin as well as exenatide reduce bodyweight in patients with type 2 diabetes. We explored the effects of dual therapy with these agents on bodyweight, body composition, glycemic parameters, and systolic blood pressure (SBP) in obese nondiabetic adults. MATERIALS AND METHODS: This single-center, double-blind trial randomized 50 obese nondiabetic adults (aged 18-70 years; body mass index 30-45 kg/m(2) ) to oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo...
August 23, 2016: Diabetes, Obesity & Metabolism
Jamie Wroge, Nancy Toedter Williams
OBJECTIVE: To evaluate the literature about the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of cardiac disorders, specifically myocardial infarction (MI) and heart failure (HF). DATA SOURCES: Searches were conducted in MEDLINE (1946-May 2016) and Excerpta Medica (1980-May 2016) using EMBASE with the search terms glucagon-like peptide 1, exenatide, albiglutide, liraglutide, dulaglutide, myocardial infarction, heart failure, and cardiovascular The references of relevant articles were reviewed to identify additional citations...
August 16, 2016: Annals of Pharmacotherapy
Juan P Frías, Samer Nakhle, James A Ruggles, Sergey Zhuplatov, Eric Klein, Rong Zhou, Poul Strange
AIM: To assess the effects of once-weekly exenatide on 24-hour glucose control and variability. MATERIALS AND METHODS: This double-blind, placebo-controlled trial randomized metformin-treated adults with type 2 diabetes to once-weekly exenatide 2.0 mg or placebo. Continuous glucose monitoring (CGM) was performed at baseline and weeks 4 and 10. The primary outcome was change in CGM-measured 24-hour mean glucose level. RESULTS: In the once-weekly exenatide (n = 60) and placebo (n = 56) groups (modified intention-to-treat population), the baseline glycated haemoglobin (HbA1c) concentrations were 8...
August 16, 2016: Diabetes, Obesity & Metabolism
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