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https://www.readbyqxmd.com/read/28213092/prediction-of-thyroid-c-cell-carcinogenicity-after-chronic-administration-of-glp1-r-agonists-in-rodents
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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-glp-1-receptor-agonists-incidences-and-consequences
#7
Michael Horowitz, Vanita R Aroda, Jenny Han, Elise Hardy, Chris K Rayner
AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with gastrointestinal adverse events (AEs), although type and frequency may differ across the class. We characterized gastrointestinal AEs with different GLP-1RAs. METHODS: Two retrospective intent-to-treat analyses of 6-month patient-level data were conducted. Data from three studies comparing exenatide once weekly (QW; n = 617) with exenatide twice daily (BID; n = 606) were pooled, and one (DURATION-6) comparing exenatide QW (n = 461) with liraglutide (n = 450) was analyzed 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
#8
Tatiana Dilla, Dimitra Alexiou, Ismini Chatzitheofilou, Ruba Ayyub, Julia Lowin, Kirsi Norrbacka
OBJECTIVE: Dulaglutide 1.5mg 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 versus liraglutide 1.8mg 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...
December 23, 2016: 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
#9
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
#10
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
#11
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...
December 11, 2016: 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
#12
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
#13
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
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
#14
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 aim of this study was to assess the risk of adverse events (AEs) with GLP-1 RAs and their relation to dose, background medication and duration of action. RESEARCH DESIGN 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/27797785/glucagon-like-peptide-1-analogues-and-risk-of-breast-cancer-in-women-with-type-2-diabetes-population-based-cohort-study-using-the-uk-clinical-practice-research-datalink
#15
Blánaid M Hicks, Hui Yin, Oriana H Y Yu, Michael N Pollak, Robert W Platt, Laurent Azoulay
OBJECTIVE:  To determine whether the use of glucagon-like peptide-1 (GLP-1) analogues, compared with the use of dipeptidylpeptidase-4 (DPP-4) inhibitors, is associated with an increased risk of incident breast cancer in patients with type 2 diabetes. DESIGN:  Population based cohort study. SETTING:  Clinical Practice Research Datalink, UK. PARTICIPANTS:  44 984 women aged at least 40 years, who were newly treated with glucose lowering drugs between 1 January 2007 and 31 March 2015, with follow-up until 31 March 2016...
October 20, 2016: BMJ: British Medical Journal
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 Y M 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...
February 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27704740/correlation-of-glypican-4-level-with-basal-active-glucagon-like-peptide-1-level-in-patients-with-type-2-diabetes-mellitus
#17
Sang Ah Lee, Gwanpyo Koh, Suk Ju Cho, So Yeon Yoo, Sang Ouk Chin
BACKGROUND: Previous studies have reported that glypican-4 (GPC4) regulates insulin signaling by interacting with insulin receptor and through adipocyte differentiation. However, GPC4 has not been studied with regard to its effects on clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to identify factors associated with GPC4 level in T2DM. METHODS: Between January 2010 and December 2013, we selected 152 subjects with T2DM and collected serum and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4 inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)...
September 2016: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27696231/combination-therapy-with-glp-1-analogues-and-sglt-2-inhibitors-in-the-management-of-diabesity-the-real-world-experience
#18
Herpreet Deol, Leoni Lekkakou, Ananth K Viswanath, Joseph M Pappachan
Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre...
January 2017: Endocrine
https://www.readbyqxmd.com/read/27663542/serum-fasting-glp-1-and-glp-2-associate-with-intestinal-adaptation-in-pediatric-onset-intestinal-failure
#19
Annika Mutanen, Mikko P Pakarinen
AIM: Glukagon-like-peptide-1 (GLP-1) and -2 (GLP-2), produced by intestinal L-cells, are key hormones regulating intestinal transit, secretion, absorption, and mucosal growth. We evaluated naïve fasting serum GLP-1 and GLP-2 levels in pediatric intestinal failure (IF). METHODS: Fifty-five IF patients with median age 4.2 (IQR 1.3-12) years and 47 matched healthy controls underwent measurement of fasting serum GLP-1 and GLP-2. RESULTS: Serum GLP-2 [19...
September 14, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27651331/exenatide-once-weekly-plus-dapagliflozin-once-daily-versus-exenatide-or-dapagliflozin-alone-in-patients-with-type-2-diabetes-inadequately-controlled-with-metformin-monotherapy-duration-8-a-28-week-multicentre-double-blind-phase-3-randomised-controlled-trial
#20
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...
December 2016: Lancet Diabetes & Endocrinology
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