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https://www.readbyqxmd.com/read/28501352/effects-of-glucagon-like-peptide-1-receptor-agonists-on-mortality-and-cardiovascular-events-a-comprehensive-meta-analysis-of-randomized-controlled-trials
#1
Matteo Monami, Stefania Zannoni, Laura Pala, Antonio Silverii, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
INTRODUCTION: The publication of the results of LEADER and SUSTAIN-6 trials suggested a possible beneficial effect of the class of GLP-1 receptor agonists on cardiovascular morbidity and mortality. The aim of the present meta-analysis is to collect and synthetize all available evidence on the effect of GLP-1 receptor agonists on cardiovascular events and mortality. METHODS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration >11weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug...
May 5, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28489279/dipeptidyl-peptidase-dpp-4-inhibitors-and-glucagon-like-peptide-glp-1-analogues-for-prevention-or-delay-of-type-2-diabetes-mellitus-and-its-associated-complications-in-people-at-increased-risk-for-the-development-of-type-2-diabetes-mellitus
#2
REVIEW
Bianca Hemmingsen, David P Sonne, Maria-Inti Metzendorf, Bernd Richter
BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown. OBJECTIVES: To assess the effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these...
May 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28479155/treatment-with-glp1-receptor-agonists-reduce-serum-crp-concentrations-in-patients-with-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#3
REVIEW
Mohsen Mazidi, Ehsan Karimi, Peyman Rezaie, Gordon A Ferns
AIM: To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations. METHOD: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched for the period up until March 16, 2016. Prospective studies evaluating the impact of GLP-1 RAs on serum CRP were identified. A random effects model (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis...
May 30, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28462078/monomeric-glp-1-gip-glucagon-triagonism-corrects-obesity-hepatosteatosis-and-dyslipidemia-in-female-mice
#4
Sigrid Jall, Stephan Sachs, Christoffer Clemmensen, Brian Finan, Frauke Neff, Richard D DiMarchi, Matthias H Tschöp, Timo D Müller, Susanna M Hofmann
OBJECTIVE: Obesity is a major health threat that affects men and women equally. Despite this fact, weight-loss potential of pharmacotherapies is typically first evaluated in male mouse models of diet-induced obesity (DIO). To address this disparity we herein determined whether a monomeric peptide with agonism at the receptors for glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon is equally efficient in correcting DIO, dyslipidemia, and glucose metabolism in DIO female mice as it has been previously established for DIO male mice...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28454792/baseline-characteristics-of-patients-enrolled-in-the-exenatide-study-of-cardiovascular-event-lowering-exscel
#5
Robert J Mentz, M Angelyn Bethel, Stephanie Gustavson, Vivian P Thompson, Neha J Pagidipati, John B Buse, Juliana C Chan, Nayyar Iqbal, Aldo P Maggioni, Steve P Marso, Peter Ohman, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez, Rury R Holman
BACKGROUND: EXSCEL is a randomized, double-blind, placebo-controlled trial examining the effect of exenatide once-weekly (EQW) versus placebo on time to the primary composite outcome (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in patients with type 2 diabetes mellitus (DM) and a wide range of cardiovascular (CV) risk. METHODS: Patients were enrolled at 688 sites in 35 countries. We describe their baseline characteristics according to prior CV event status and compare patients with those enrolled in prior glucagon-like peptide-1 receptor agonist (GLP-1RA) outcomes trials...
May 2017: American Heart Journal
https://www.readbyqxmd.com/read/28452143/zy15557-a-novel-long-acting-dpp-4-inhibitor-for-the-treatment-of-type-2-diabetes-mellitus
#6
M R Jain, A A Joharapurkar, S G Kshirsagar, V J Patel, R H Bahekar, H V Patel, P A Jadav, P R Patel, R C Desai
BACKGROUND AND PURPOSE: Dipeptidylpeptidase 4 (DPP-4) inhibitors increase levels of glucagon-like peptide -1 (GLP-1) and provide clinical benefit in the treatment of type 2 diabetes mellitus. Since longer acting inhibitors have therapeutic advantage, we developed a novel DPP-4 inhibitor, ZY15557 that has a sustained action and long half-life. EXPERIMENTAL APPROACH: We studied the potency, selectivity, efficacy and duration of action of ZY15557 using in vitro and in vivo preclinical models...
April 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28435446/cardiovascular-risk-assessment-in-patients-with-diabetes
#7
REVIEW
Marcello Casaccia Bertoluci, Viviane Zorzanelli Rocha
Although patients with diabetes have 2 to 4 times increased risk of cardiovascular morbidity and mortality than individuals without diabetes, recent studies indicate that a significant part of patients are in a lower cardiovascular risk category. Men younger than 35 years, women younger than 45 years, patients with diabetes duration of less than 10 years without other risk factors have a much lower risk than patients who have traditional cardiovascular risk factors, and subclinical or established coronary artery disease (CAD)...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28398946/high-intensity-interval-training-appetite-and-reward-value-of-food-in-the-obese
#8
Catia Martins, Irina Aschehoug, Marit Ludviksen, Jens Holst, Graham Finlayson, Ulrik Wisloff, Linda Morgan, Neil King, Bård Kulseng
PURPOSE: Studies on the impact of chronic interval training on appetite in the obese population are scarce. The aim of this study was to determine the effect of 12 weeks of isocaloric programs of moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT), or a short-duration HIIT (1/2HIIT), on subjective feelings of appetite, appetite-related hormones and reward value of food in sedentary obese individuals. METHODS: Forty-six sedentary obese individuals (30 women and 16 men), with a BMI of 33...
April 11, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28351296/regulatory-forum-opinion-piece
#9
Sherry J Morgan, Jessica Couch, Peggy Guzzie-Peck, Douglas A Keller, Ray Kemper, Monicah A Otieno, Robert J Schulingkamp, Thomas W Jones
An Innovation and Quality (IQ) Consortium focus group conducted a cross-company survey to evaluate current practices and perceptions around the use of animal models of disease (AMDs) in nonclinical safety assessment of molecules in clinical development. The IQ Consortium group is an organization of pharmaceutical and biotechnology companies with the mission of advancing science and technology. The survey queried the utilization of AMDs during drug discovery in which drug candidates are evaluated in efficacy models and limited short-duration non-Good Laboratory Practices (GLP) toxicology testing and during drug development in which drug candidates are evaluated in GLP toxicology studies...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28349716/fixed-ratio-combination-therapy-with-glp-1-receptor-agonist-liraglutide-and-insulin-degludec-in-people-with-type-2-diabetes
#10
Lauge Østergaard, Christian Seerup Frandsen, Thomas Fremming Dejgaard, Sten Madsbad
A fixed combination of basal insulin degludec and glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (IDegLira; 50 units degludec/1.8 mg liraglutide) has been developed as a once daily injection for the treatment of type 2 diabetes (T2D). In the phase 3a trial programme 'Dual action of liraglutide and insulin degludec in type 2 diabetes' (DUAL™), five trials of 26 weeks duration and one trial of 32 weeks duration have evaluated the efficacy and safety of IDegLira compared with administration of insulin degludec, insulin glargine, liraglutide alone or placebo...
June 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28342399/design-synthesis-and-biological-evaluation-of-pegylated-xenopus-glucagon-like-peptide-1-derivatives-as-long-acting-hypoglycemic-agents
#11
Jing Han, Yiyun Wang, Qinghua Meng, Guangchao Li, Fangmin Huang, Su Wu, Yingying Fei, Feng Zhou, Junjie Fu
In order to develop novel long-acting GLP-1 derivatives, a peptide hybrid (1a) from human GLP-1 and Xenopus GLP-1 discovered in our previous research was selected as the lead compound. Exendin-4 inspired modification resulted in peptide 1b with enhanced glucose-lowering activity. Cysteine mutated 1b derivatives with reserved bioactivity were further site-specifically connected with mPEG2000-MAL to provide conjugates 3a-h, among which 3d and 3e were found to have significantly improved hypoglycemic activity and insulinotropic ability than GLP-1...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28331351/long-term-management-of-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists
#12
REVIEW
Hamish Courtney, Rahul Nayar, Chinnadorai Rajeswaran, Ravi Jandhyala
Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28318688/impact-of-phenylketonuria-type-meal-on-appetite-thermic-effect-of-feeding-and-postprandial-fat-oxidation
#13
Hani Alfheeaid, Konstantinos Gerasimidis, Ana-Maria Năstase, Mie Elhauge, Barbara Cochrane, Dalia Malkova
BACKGROUND: Dietary management of phenylketonuria (PKU) requires the replacement of natural protein-containing foods with special low protein foods. The effect of a PKU type diet on factors contributing to energy balance requires investigation. OBJECTIVE: To investigate the impact of a PKU type meal on appetite ratings, gut appetite hormones, thermic effect of feeding (TEF) and fat oxidation. METHODS: Twenty-three healthy adults (mean ± SD age: 24...
March 8, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28298900/the-impact-of-bariatric-surgery-on-type-2-diabetes-mellitus-and-the-management-of-hypoglycemic-events
#14
REVIEW
Mahmoud Attia Mohamed Kassem, Michael Andrew Durda, Nicoleta Stoicea, Omer Cavus, Levent Sahin, Barbara Rogers
Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28276778/glp-1-receptor-agonists-in-the-treatment-of-polycystic-ovary-syndrome
#15
REVIEW
Elizabeth Mary Lamos, Rana Malek, Stephen N Davis
Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed...
April 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28265415/metabolic-improvements-following-roux-en-y-surgery-assessed-by-solid-meal-test-in-subjects-with-short-duration-type-2-diabetes
#16
Sudha S Shankar, Lori A Mixson, Manu Chakravarthy, Robin Chisholm, Anthony J Acton, RoseMarie Jones, Samer G Mattar, Deborah L Miller, Lea Petry, Chan R Beals, S Aubrey Stoch, David E Kelley, Robert V Considine
BACKGROUND: Glucose homeostasis improves within days following Roux-en-Y gastric bypass (RYGB) surgery. The dynamic metabolic response to caloric intake following RYGB has been assessed using liquid mixed meal tolerance tests (MMTT). Few studies have evaluated the glycemic and hormonal response to a solid mixed meal in subjects with diabetes prior to, and within the first month following RYGB. METHODS: Seventeen women with type 2 diabetes of less than 5 years duration participated...
2017: BMC Obesity
https://www.readbyqxmd.com/read/28244632/safety-issues-with-glucagon-like-peptide-1-receptor-agonists-pancreatitis-pancreatic-cancer-and-cholelithiasis-data-from-randomised-controlled-trials
#17
Matteo Monami, Besmir Nreu, Alessia Scatena, Barbara Cresci, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
AIM: Glucagon-like Peptide 1 Receptor Agonists (GLP1-RA) has been associated with an increased risk of pancreatitis and pancreatic cancer. Prior meta-analyses of randomized controlled trials failed to show any significant increase of risk; however, those meta-analyses did not include the recently published cardiovascular outcome trials (CVOT) with GLP1-RA, which provide a substantial additional body of data. The aim of the present meta-analysis is to assess the effect of GLP1-RA on pancreatitis, pancreatic cancers and cholelithiasis...
February 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#18
Willem van den Brink, Annette Emerenciana, Francesco Bellanti, Oscar Della Pasqua, Jan Willem van der Laan
Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products...
February 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28181363/chronic-liraglutide-therapy-induces-an-enhanced-endogenous-glucagon-like-peptide-1-secretory-response-in-early-type-2-diabetes
#19
Caroline K Kramer, Bernard Zinman, Haysook Choi, Philip W Connelly, Ravi Retnakaran
Sustained exogenous stimulation of a hormone-specific receptor can affect endogenous hormonal regulation. In this context, little is known about the impact of chronic treatment with glucagon-like peptide-1 (GLP-1) agonists on the endogenous GLP-1 response. We therefore evaluated the impact of chronic liraglutide therapy on endogenous GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) response to an oral glucose challenge. A total of 51 people with type 2 diabetes of 2.6 ± 1.9 years' duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48 weeks, with an oral glucose tolerance test (OGTT) every 12 weeks...
February 9, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28176959/a-systematic-literature-review-on-the-efficacy-effectiveness-gap-comparison-of-randomized-controlled-trials-and-observational-studies-of-glucose-lowering-drugs
#20
REVIEW
Mikkel Z Ankarfeldt, Erpur Adalsteinsson, Rolf Hh Groenwold, M Sanni Ali, Olaf H Klungel
AIM: To identify a potential efficacy-effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. METHODS: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome...
2017: Clinical Epidemiology
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