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https://www.readbyqxmd.com/read/28342399/design-synthesis-and-biological-evaluation-of-pegylated-xenopus-glucagon-like-peptide-1-derivatives-as-long-acting-hypoglycemic-agents
#1
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
#2
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
#3
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
#4
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
#5
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...
February 13, 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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28161122/acute-and-repeated-dose-28-days-toxicity-studies-in-rats-and-dogs-of-recombinant-batroxobin-a-snake-venom-thrombin-like-enzyme-expressed-from-pichia-pastoris
#11
Ok Hwan Kim, Kil-Sang Cho, Young Seomun, Jong-Tak Kim, Kwang-Hoe Chung
Recombinant batroxobin is a thrombin-like enzyme of Bothrops atrox moojeni venom. To evaluate its toxicological effect, it was highly expressed in Pichia pastorisand successfully purified to homogeneity from culture broth supernatant following Good Manufacturing Practice (GMP). The maximum tolerated dose of the recombinant batroxobin was examined in Sprague-Dawley (SD) rat and Beagle dogs following Good Laboratory Practice (GLP) regulations. The approximate lethal dose of recombinant batroxobin was 10 National Institute of Health (NIH) u/kg in male and female rats...
February 1, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28106956/comparisons-of-weight-changes-between-sglt2-inhibitors-treatment-and-glp-1-analogs-treatment-in-type-2-diabetes-patients-a-meta-analysis
#12
REVIEW
Xiaoling Cai, Liwei Ji, Yifei Chen, Wenjia Yang, Lingli Zhou, Xueyao Han, Simin Zhang, Linong Ji
To evaluate the efficacy of weight changes from baseline of the SGLT2 inhibitors treatment and GLP-1 analogs treatment after comparisons with placebo in type 2 diabetes patients and the associated factors MATERIALS AND METHODS: Studies were searched from when recording began, June 2004, until June 2015, and re-searched on July 2016, and placebo-controlled randomized trials in type 2 diabetes patients with a study length ≥12 weeks were included RESULTS: A total of 97 RCTs were included. Compared with placebo, treatment with SGLT2 inhibitors was associated with a significant greater decrease in weight change from baseline, (weighted mean differences (WMD), -2...
January 20, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28086882/differential-effects-of-glucagon-like-peptide-1-receptor-agonists-on-heart-rate
#13
REVIEW
Martin Lorenz, Francesca Lawson, David Owens, Denis Raccah, Christine Roy-Duval, Anne Lehmann, Riccardo Perfetti, Lawrence Blonde
While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms)...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28058769/upper-and-or-lower-gastrointestinal-adverse-events-with-glucagon-like-peptide-1-receptor-agonists-incidence-and-consequences
#14
Michael Horowitz, Vanita R Aroda, Jenny Han, Elise Hardy, Chris K Rayner
AIMS: To characterize gastrointestinal adverse events (AEs) with different glucagon-like peptide-1 receptor agonists (GLP-1RAs). METHODS: Two retrospective intention-to-treat analyses of 6-month patient-level data were conducted. Data from three studies comparing exenatide once weekly (n = 617) with exenatide twice daily (n = 606) were pooled, and one (DURATION-6) comparing exenatide once weekly (n = 461) with liraglutide (n = 450) was analysed separately...
January 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28008768/the-cost-effectiveness-of-dulaglutide-versus-liraglutide-for-the-treatment-of-type-2-diabetes-mellitus-in-spain-in-patients-with-bmi-%C3%A2-30%C3%A2-kg-m-2
#15
Tatiana Dilla, Dimitra Alexiou, Ismini Chatzitheofilou, Ruba Ayyub, Julia Lowin, Kirsi Norrbacka
OBJECTIVE: Dulaglutide 1.5 mg once weekly is a novel glucagon-like peptide 1 (GLP-1) receptor agonist, for the treatment of type two diabetes mellitus (T2DM). The objective was to estimate the cost-effectiveness of dulaglutide once weekly vs liraglutide 1.8 mg once daily for the treatment of T2DM in Spain in patients with a BMI ≥30 kg/m(2). METHODS: The IMS CORE Diabetes Model (CDM) was used to estimate costs and outcomes from the perspective of Spanish National Health System, capturing relevant direct medical costs over a lifetime time horizon...
January 13, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28003008/glucagon-like-peptide-1-glp-1-receptor-agonists-in-the-treatment-of-obese-women-with-polycystic-ovary-syndrome
#16
Themistoklis Tzotzas, Spyridon N Karras, Niki Katsiki
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females and is often associated with a number of cardiometabolic disorders such as central obesity, dyslipidaemia, hypertension, insulin resistance, hyperinsulinaemia, glucose intolerance and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1), a gut hormone secreted after a meal, enhances glucose-stimulated insulin secretion and additionally suppresses appetite and gastric motility. Most studies found impaired GLP-1 kinetics in obese individuals, whereas small studies in PCOS reported reduced, normal or even elevated GLP-1 levels...
December 21, 2016: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/27942008/the-dpp4-inhibitor-linagliptin-protects-from-experimental-diabetic-retinopathy
#17
Nadine Dietrich, Matthias Kolibabka, Stephanie Busch, Petra Bugert, Ulrike Kaiser, Jihong Lin, Thomas Fleming, Michael Morcos, Thomas Klein, Andrea Schlotterer, Hans-Peter Hammes
BACKGROUND/AIMS: Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. METHODS: Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1...
2016: PloS One
https://www.readbyqxmd.com/read/27924636/safety-and-tolerability-of-glucagon-like-peptide-1-receptor-agonists-unresolved-and-emerging-issues
#18
REVIEW
Denis Raccah
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a mainstay of treatment options for type 2 diabetes. They contribute to lowering blood glucose levels, generally have a favorable tolerability profile, and can be used alone or in combination with other antidiabetic agents. Based on the duration of their effects, GLP-1 RAs can be divided into two classes: short-acting and long-acting. Differences exist between these sub-classes, and between each drug, in terms of pharmacokinetic and pharmacodynamic profiles...
February 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27913575/lowest-glucose-variability-and-hypoglycemia-are-observed-with-the-combination-of-a-glp-1-receptor-agonist-and-basal-insulin-variation-study
#19
Harpreet S Bajaj, Karri Venn, Chenglin Ye, Avril Patrick, Shivani Kalra, Hasnain Khandwala, Nadeem Aslam, David Twum-Barima, Ronnie Aronson
OBJECTIVE: There is a dearth of published literature comparing glucose variability (GV) between different insulin regimens in type 2 diabetes. This cohort study compares GV using continuous glucose monitoring (CGM) in patients with well-controlled type 2 diabetes using four common insulin regimens: basal insulin + oral drugs (BO), basal insulin + glucagon-like peptide 1 receptor agonist (GLP-1 RA) (BGLP), premixed insulin (PM), and basal-bolus insulin (BB). RESEARCH DESIGN AND METHODS: Consecutive patients from three endocrinology clinics who met study criteria-type 2 diabetes, age 18 to 80 years, BMI ≤ 45 kg/m(2), stable insulin regimen for a minimum of 6 months, and stable A1C value ≤7...
February 2017: Diabetes Care
https://www.readbyqxmd.com/read/27881129/impact-of-dipeptidyl-peptidase-4-inhibitors-on-serum-adiponectin-a-meta-analysis
#20
Xin Liu, Peng Men, Yuhui Wang, Suodi Zhai, George Liu
BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1)...
November 23, 2016: Lipids in Health and Disease
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