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https://www.readbyqxmd.com/read/27921428/-promising-molecules-for-treatment-of-hyperglycemia-in-patients-with-type-2-diabetes
#1
Milan Kvapil
New antidiabetic drugs are being developed today that expand the range of pharmacological intervention, in particular for patients with type 2 diabetes (imeglimin, semaglutide, dulaglutide, FGF 21 analogue). At the same time innovations take place that "better" the well-proven molecules, they offer new application forms we have no experience of diabetology (osmotic pump for exenatide, faster acting insulin aspart). New properties are brought by just the change of concentration (insulin glargine in a concentration of 300 U/ml), unexpected positive results are also brought by new fixed-ratio combinations of antidiabetics (fixed-ratio combination of insulin degludec and liraglutide, fixed-ratio combination of insulin glargine and lixisenatide)...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27899001/drug-interventions-for-the-treatment-of-obesity-in-children-and-adolescents
#2
REVIEW
Emma Mead, Greg Atkinson, Bernd Richter, Maria-Inti Metzendorf, Louise Baur, Nicholas Finer, Eva Corpeleijn, Claire O'Malley, Louisa J Ells
BACKGROUND: Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. OBJECTIVES: To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016...
November 29, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27898183/effect-of-exenatide-on-postprandial-glucose-fluxes-lipolysis-and-%C3%A3-cell-function-in-nondiabetic-morbidly-obese-patients
#3
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
https://www.readbyqxmd.com/read/27896683/population-pharmacokinetics-of-an-extended-release-formulation-of-exenatide-following-single-and-multiple-dose-administration
#4
Brenda Cirincione, Jeffrey Edwards, Donald E Mager
Exenatide is a glucagon-like peptide-1 receptor agonist with both immediate- and extended-release (ER) formulations that are approved for the treatment of type 2 diabetes mellitus. Long-term exposure from the ER formulation is achieved through slow peptide release from a degradable microsphere formulation. The goal of this analysis was to develop a pharmacokinetic model for the ER formulation following single and once-weekly multiple-dose administration. Pharmacokinetic data were collected from two clinical trials-one that evaluated single-dose administration of 2...
November 28, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27891769/exenatide-induces-an-increase-in-vasodilatory-and-a-decrease-in-vasoconstrictive-mediators
#5
Ajay Chaudhuri, Husam Ghanim, Antoine Makdissi, Kelly Green, Sanaa Abuaysheh, Manav Batra, Nitesh Kuhadiya, Paresh Dandona
In view of the known vasodilatory effects of GLP-1, and exenatide, we investigated the effects of exenatide on vasoactive factors. We analyzed blood samples and mononuclear cells (MNC) from a previous study collected after a single dose and following 12 weeks of exenatide or placebo treatment on a series of 24 patients with T2DM. Following exenatide, plasma concentrations of ANP, cGMP, cAMP increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNC increased significantly following single dose...
November 28, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27889301/glycemic-control-and-weight-outcomes-for-exenatide-once-weekly-versus-liraglutide-in-patients-with-type-2-diabetes-a-1-year-retrospective-cohort-analysis
#6
Carrie McAdam-Marx, Hiep Nguyen, Marisa B Schauerhamer, Mukul Singhal, Sudhir Unni, Xiangyang Ye, David Cobden
PURPOSE: Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited information on exenatide QW or liraglutide response by glycemic control and insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA1c) and weight outcomes with exenatide QW and liraglutide in the real-world setting overall and in insulin-naive patients with uncontrolled T2D...
November 23, 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27884660/exenatide-improves-diastolic-function-and-attenuates-arterial-stiffness-but-does-not-alter-exercise-capacity-in-individuals-with-type-2-diabetes
#7
Rebecca L Scalzo, Kerrie L Moreau, Cemal Ozemek, Leah Herlache, Shawna McMillin, Sarah Gilligan, Amy G Huebschmann, Tim A Bauer, Jennifer Dorosz, Jane E B Reusch, Judith G Regensteiner
BACKGROUND: Exercise is recommended as a cornerstone of treatment for type 2 diabetes mellitus (T2DM), however, it is often poorly adopted by patients. Even in the absence of apparent cardiovascular disease, persons with T2DM have an impaired ability to carry out maximal and submaximal exercise and these impairments are correlated with cardiac and endothelial dysfunction. Glucagon-like pepetide-1 (GLP-1) augments endothelial and cardiac function in T2DM. We hypothesized that administration of a GLP-1 agonist (exenatide) would improve exercise capacity in T2DM...
October 7, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27860132/occurrence-of-nausea-vomiting-and-diarrhoea-reported-as-adverse-events-in-clinical-trials-studying-glucagon-like-peptide-1-receptor-agonists-a-systematic-analysis-of-published-clinical-trials
#8
Karolin Bettge, Melanie Kahle, Mirna S Abd El Aziz, Juris J Meier, Michael A Nauck
AIM: GLP-1 receptor agonists (RAs) may cause nausea, vomiting or diarrhoea. The purpose was to assess the risk of adverse events (AEs) with GLP-1 RAs and their relation to dose, background medication and duration of action. MATERIAL AND METHODS: The PubMed database was searched and 32 clinical trials with GLP-1 RAs (phase 3) were selected. We performed a systematic analysis and compared the proportion of patients reporting nausea, vomiting or diarrhoea, for different doses and glucose-lowering background medications, and relative to a reference compound within the subclasses of short- (exenatide b...
November 9, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27856826/the-influence-of-varying-cost-formats-on-preferences
#9
Charles Changchuan Jiang, Liana Fraenkel
BACKGROUND: Numerous studies have found that cost strongly influences patients' decision making. The objective of this study was to explore the impact of varying cost formats on patients' preferences. METHODS: Mechanical Turk workers completed a choice-based conjoint (CBC) survey. The CBC survey was designed to examine stated preferences for the use of second-line agents to treat diabetes across 5 attributes: route of administration, efficacy, risk of low blood sugar, frequency of checking blood sugar levels, and cost...
January 2017: Medical Decision Making: An International Journal of the Society for Medical Decision Making
https://www.readbyqxmd.com/read/27832452/clinical-pharmacokinetics-and-pharmacodynamics-of-antihyperglycemic-medications-in-children-and-adolescents-with-type-2-diabetes-mellitus
#10
REVIEW
Fatemeh Akhlaghi, Kelly L Matson, Amir Hooshang Mohammadpour, Meghan Kelly, Asieh Karimani
The incidence of type 2 diabetes mellitus (T2DM) among children and adolescents has been rising. This condition is associated with obesity, and it's prevalence is higher among minority or female youth. Lifestyle modification including diet and exercise is only successful in a small proportion of patients; therefore, pharmacotherapy approaches are needed to treat T2DM among youth. Currently, in the USA, only metformin and insulin are approved for the treatment of T2DM in children. However, several antihyperglycemic agents including exenatide, glimepiride, glyburide, liraglutide, pioglitazone, and rosiglitazone are also used off-label in this population...
November 10, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27777261/heart-rate-acceleration-with-glp-1-receptor-agonists-in-type-2-diabetes-patients-an-acute-and-12-week-randomised-double-blind-placebo-controlled-trial
#11
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mhh Kramer, Michaela Diamant, Daniël H van Raalte
OBJECTIVE: To examine mechanisms underlying resting heart rate (RHR) increments of GLP-1 receptor agonists in type 2 diabetes patients. DESIGN: Acute and 12-week randomised placebo-controlled, double-blind, single-centre parallel-group trial. METHODS: 57 type 2 diabetes patients (mean±SD age 62.8±6.9 years; BMI 31.8±4.1 kg/m2; HbA1c 7.3±0.6%), treated with metformin and/or sulfonylureas, were included between July 2013 and August 2015...
October 24, 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27776251/the-effects-of-exenatide-twice-daily-compared-to-insulin-lispro-added-to-basal-insulin-in-latin-american-patients-with-type-2-diabetes-a-retrospective-analysis-of-the-4b-trial
#12
Silvia Beatriz Gorban de Lapertosa, Gustavo Frechtel, Elise Hardy, Leobardo Sauque-Reyna
AIMS: Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. METHODS: This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin...
October 8, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27766579/a-plethora-of-glp-1-agonists-decisions-about-what-to-use-and-when
#13
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
https://www.readbyqxmd.com/read/27743854/exenatide-prevents-morphological-and-structural-changes-of-mitochondria-following-ischaemia-reperfusion-injury
#14
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
https://www.readbyqxmd.com/read/27717222/effect-of-glp-1-receptor-agonist-treatment-on-body-weight-in-obese-antipsychotic-treated-patients-with-schizophrenia-a-randomized-placebo-controlled-trial-byline
#15
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
https://www.readbyqxmd.com/read/27717130/glucagon-like-peptide-1-receptor-agonists-compared-with-basal-insulins-for-the-treatment-of-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis
#16
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
https://www.readbyqxmd.com/read/27702762/attenuation-of-carotid-neointimal-formation-after-direct-delivery-of-a-recombinant-adenovirus-expressing-glucagon-like-peptide-1-in-diabetic-rats
#17
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
https://www.readbyqxmd.com/read/27691959/treatment-of-diabetes-mellitus-in-a-golden-lion-tamarin-leontopithecus-rosalia-with-the-glucagon-like-peptide-1-mimetic-exenatide
#18
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
https://www.readbyqxmd.com/read/27669277/the-use-of-exenatide-in-managing-markers-of-cardiovascular-risk-in-patients-with-type-2-diabetes-a-systematic-review
#19
REVIEW
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
https://www.readbyqxmd.com/read/27658750/exenatide-substantially-improves-proinsulin-conversion-and-cell-survival-that-augment-ins2-akita-beta-cell-function
#20
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
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