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https://www.readbyqxmd.com/read/29239601/preparation-and-pharmaceutical-characterizations-of-lipidated-dimeric-xenopus-glucagon-like-peptide-1-conjugates
#1
Jing Han, Feng Zhou, Yingying Fei, Xinyu Chen, Junjie Fu, Hai Qian
Two glucagon-like peptide-1 (GLP-1) analogs (1 and 2) were synthesized by hybridizing the key sequences of GLP-1, exendin-4, lixisenatide and xenGLP-1B (Xenopus GLP-1 analog). To achieve long-acting hypoglycemic effects and to further improve their antidiabetic potencies, lipidization and dimerization strategies were used to afford two lipidated dimeric conjugates (9 and 11). Conjugates 9 and 11 showed stronger receptor activation potency than GLP-1 and exendin-4 in vitro. Moreover, 9 and 11 exhibited superior hypoglycemic and insulinotropic activities to liraglutide in db/db mice...
December 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29235507/blood-brain-glucose-transfer-in-alzheimer-s-disease-effect-of-glp-1-analog-treatment
#2
Michael Gejl, Birgitte Brock, Lærke Egefjord, Kim Vang, Jørgen Rungby, Albert Gjedde
There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29205774/comparison-of-glucose-lowering-agents-following-dual-therapy-failure-in-type-2-diabetes-systematic-review-and-network-meta-analysis-of-randomised-controlled-trials
#3
Francesco Zaccardi, Nafeesa N Dhalwani, Jolyon Dales, Hamid Mani, Kamlesh Khunti, Melanie J Davies, David R Webb
AIMS: To assess the evidence supporting the choice of third-line agents in adults with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: We searched RCTs published between Jan 2000 and July 2017 reporting data on cardiometabolic outcomes and hypoglycaemia for glucose-lowering agents added to metformin-based dual treatments. Data were stratified by background therapy and RCT duration and synthesised, when possible, with network meta-analyses. RESULTS: 43 RCTs (16590 participants) were included, with metformin combined to sulphonylurea (SU) in 20 RCTs; thiazolidinedione (TZD) in 10; basal or rapid acting insulin in 6; DPP-4i in 3; GLP-1RA in 2; and SGLT-2i in 2...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29183873/effect-of-chronic-liraglutide-therapy-and-its-withdrawal-on-time-to-post-challenge-peak-glucose-in-patients-with-type-2-diabetes
#4
Susan Tran, Caroline K Kramer, Bernard Zinman, Haysook Choi, Ravi Retnakaran
Delayed timing of peak serum glucose following an oral glucose challenge can predict declining beta-cell function and worsening glucose tolerance over time. Accordingly, post-challenge peak glucose is typically delayed in patients with type 2 diabetes (T2DM). However, little is known about the capacity of anti-diabetic medications to reverse this delay. Thus, we sought to evaluate the effect of the glucagon-like peptide-1 (GLP-1) agonist liraglutide on time to peak glucose in early T2DM. In this secondary analysis of a double-blind, placebo-controlled trial, 51 patients with T2DM of 2...
November 28, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29180139/combined-gastrin-releasing-peptide-29-and-glucagon-like-peptide-1-reduce-body-weight-more-than-each-individual-peptide-in-diet-induced-obese-male-rats
#5
Thaer R Mhalhal, Martha C Washington, Kayla D Newman, John C Heath, Ayman I Sayegh
To test the hypothesis that gastrin releasing peptide-29 (GRP-29) combined with glucagon like peptide-1 (7-36) (GLP-1 (7-36)) reduce body weight (BW) more than each of the peptides given individually, we infused the two peptides (0.5nmol/kg each) in the aorta of free feeding, diet-induced obese (DIO) male Sprague Dawley rats once daily for 25days and measured BW. We found that GRP-29 and GLP-1 reduce BW, GRP-29 reduced it more than GLP-1 and GRP-29+GLP-1 reduce BW more than each peptide given alone. This reduction was accompanied by decrease 24-hour food intake (normal rat chow), meal size (MS), duration of first meal and number of meals, and increase latency to the first meal, intermeal interval (IMI) and satiety ratio (IMI/MS, amount of food consumed per a unit of time)...
November 21, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29171021/xenopus-glp-1-derived-and-pegylated-glp-1-receptor-agonists-long-acting-hypoglycemic-and-insulinotropic-activities-with-potential-therapeutic-utilities
#6
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Ying Zhang, Lin Liu, Junjie Fu
BACKGROUND AND PURPOSE: Incretin-based therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists are effective methods for treating type 2 diabetes. Numerous research efforts are focused on the development of long-acting GLP-1 receptor agonists. However, all GLP-1 receptor agonists in clinical use or in clinical development are based on human GLP-1 or Gila GLP-1. We previously identified xGLP-1B as a potent GLP-1 receptor agonist based on Xenopus GLP-1. EXPERIMENTAL APPROACH: To further modify the structure of xGLP-1B, alanine scanning was performed to study the structure-activity relationship of xGLP-1B...
November 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29167470/glucagon-like-peptide-1-mimetics-optimal-for-asian-type-2-diabetes-patients-with-and-without-overweight-obesity-meta-analysis-of-randomized-controlled-trials
#7
Fang Zhang, Lizhi Tang, Yuwei Zhang, Qingguo Lü, Nanwei Tong
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes, especially in patients with overweight/obesity. We aimed to determine whether GLP-1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes (T2D) patients with and without overweight/obesity. Randomized controlled trials were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies published in English with treatment duration ≥12 weeks and information on HbA1c changes were included. The studies were divided into normal body mass index (BMI) and overweight/obese groups according to baseline BMI...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29076038/long-term-effectiveness-of-liraglutide-in-association-with-patients-baseline-characteristics-in-real-life-setting-in-croatia-an-observational-retrospective-multicenter-study
#8
Maja Cigrovski Berkovic, Ines Bilic-Curcic, Davorka Herman Mahecic, Marina Gradiser, Mladen Grgurevic, Tomislav Bozek
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are recommended therapy for type 2 diabetes (T2DM) and liraglutide is the most used worldwide. We assessed the glycemic efficacy and extra-glycemic effects of liraglutide during 36 months' follow-up of individuals with poorly regulated T2DM under routine clinical practice and sought to identify the phenotype of treatment responders. METHODS: A total of 207 individuals were included. The primary endpoint was the proportion of participants with HbA1c < 7...
December 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29072800/effect-of-sitagliptin-on-glucose-control-in-type-2-diabetes-mellitus-after-roux-en-y-gastric-bypass-surgery
#9
Ankit Shah, Kiarra Levesque, Esmeralda Pierini, Betsy Rojas, Michael Ahlers, Sarah Stano, Marlena Holter, Roxanne Dutia, Scott Belsley, James McGinty, Blandine Laferrère
This is a 4-week randomized trial to assess the efficacy and safety of sitagliptin, a dipeptidyl-peptidase-4 inhibitor, in persistent or recurring type 2 diabetes after gastric bypass surgery (RYGB). Subjects (n=32) completed a mixed meal test (MMT) and home glucose monitoring (SPMG) before and 4 weeks after randomization to either sitagliptin 100 mg daily (S) or placebo daily (P). Questionnaires were administered to assess gastrointestinal discomfort. Outcome variables were glucose, active GLP-1 and β-cell function during the MMT and glucose levels during SPMG...
October 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29049653/effect-of-oral-semaglutide-compared-with-placebo-and-subcutaneous-semaglutide-on-glycemic-control-in-patients-with-type-2-diabetes-a-randomized-clinical-trial
#10
RANDOMIZED CONTROLLED TRIAL
Melanie Davies, Thomas R Pieber, Marie-Louise Hartoft-Nielsen, Oluf K H Hansen, Serge Jabbour, Julio Rosenstock
Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection. Objectives: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes. Design, Setting, and Patients: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014...
October 17, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29047219/addition-of-dipeptidyl-peptidase-4-inhibitors-to-insulin-treatment-in-type-2-diabetes-patients-a-meta-analysis
#11
Wenjia Yang, Xiaoling Cai, Xueying Gao, Yifei Chen, Chen Ling, Linong Ji
AIMS: To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase 4 (DPP-4) inhibitors compared to combining insulin therapy with placebo or other antihyperglycaemic agents. MATERIALS AND METHODS: A literature search was conducted via electronic databases. The inclusion criteria were randomized controlled trials (RCTs) comparing the addition of DPP-4 inhibitors to insulin with the addition of placebo or other active hypoglycaemic agents to insulin therapy, study duration of no less than 12 weeks performed in type 2 diabetes patients, and the availability of outcome data to evaluate a change in the HbA1c ...
October 19, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28964791/gut-satiety-hormones-cholecystokinin-and-glucagon-like-peptide-17-36-amide-mediate-anorexia-induction-by-trichothecenes-t-2-toxin-ht-2-toxin-diacetoxyscirpenol-and-neosolaniol
#12
Jie Zhang, Shengli Liu, Hua Zhang, Yuanyuan Li, Wenda Wu, Haibin Zhang
The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-17-36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO)...
November 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28945431/micellar-nanomedicine-of-novel-fatty-acid-modified-xenopus-glucagon-like-peptide-1-improved-physicochemical-characteristics-and-therapeutic-utilities-for-type-2-diabetes
#13
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Weiwei Zheng, Junjie Fu
To develop novel long-acting antidiabetics with improved therapeutic efficacy, two glucagon-like peptide-1 (GLP-1) analogs were constructed through the hybridization of key sequences of GLP-1, xenGLP-1B, exendin-4, and lixisenatide. Hybrids 1 and 2 demonstrated enhanced in vitro and in vivo biological activities and were further site-specifically lipidized at lysine residues to achieve prolonged duration of action and less frequent administration. Compared with their native peptides, compounds 3-6 showed similar in vitro activities but impaired in vivo acute hypoglycemic potencies due to decreased aqueous solubility and retarded absorption in vivo...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28932989/predictors-of-response-to-glucagon-like-peptide-1-receptor-agonists-a-meta-analysis-and-systematic-review-of-randomized-controlled-trials
#14
Matteo Monami, Ilaria Dicembrini, Besmir Nreu, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
AIMS: The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: A Medline and Embase search for "exenatide" OR "liraglutide" OR "albiglutide" OR "dulaglutide" OR "lixisenatide" was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs...
December 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28870887/appetite-food-intake-and-gut-hormone-responses-to-intense-aerobic-exercise-of-different-duration
#15
RANDOMIZED CONTROLLED TRIAL
Adrian Holliday, Andrew Blannin
The purpose of the study is to investigate the effect of acute bouts of high-intensity aerobic exercise of differing durations on subjective appetite, food intake and appetite-associated hormones in endurance-trained males. Twelve endurance-trained males (age = 21 ± 2 years; BMI = 21.0 ± 1.6 kg/m2; VO2max = 61.6 ± 6.0 mL/kg/min) completed four trials, within a maximum 28 day period, in a counterbalanced order: resting (REST); 15 min exercise bout (15-min); 30 min exercise bout (30-min) and 45 min exercise bout (45-min)...
December 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28822051/new-basal-insulins-a-clinical-perspective-of-their-use-in-the-treatment-of-type-2-diabetes-and-novel-treatment-options-beyond-basal-insulin
#16
REVIEW
Patrick F Frias, Juan Pablo Frias
PURPOSE OF REVIEW: The purpose of this review was to review advances in basal insulin formulations and new treatment options for patients with type 2 diabetes not achieving glycemic targets despite optimized basal insulin therapy. RECENT FINDINGS: Advances in basal insulin formulations have resulted in products with increasingly favorable pharmacokinetic and pharmacodynamic properties, including flatter, peakless action profiles, less inter- and intra-patient variability, and longer duration of activity...
August 18, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28817231/effect-of-once-weekly-dulaglutide-on-hba1c-and-fasting-blood-glucose-in-patient-subpopulations-by-gender-duration-of-diabetes-and-baseline-hba1c
#17
Baptist Gallwitz, Samuel Dagogo-Jack, Vivian Thieu, Luis-Emilio Garcia-Perez, Imre Pavo, Maria Yu, Kenneth E Robertson, Nan Zhang, Francesco Giorgino
To evaluate the efficacy and safety of dulaglutide 1.5 mg and 0.75 mg in type 2 diabetes patients by subgroups of gender, duration of diabetes, and baseline HbA1c in the dulaglutide clinical development program (AWARD-1 to -6 and -8 clinical trials). MATERIALS AND METHODS: Change in HbA1c was analysed by gender, duration of diabetes (<5 years, ≥5 years and <10 years, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia, and gastrointestinal adverse events were evaluated for individual trials...
August 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28768173/the-sustained-effects-of-a-dual-gip-glp-1-receptor-agonist-nnc0090-2746-in-patients-with-type-2-diabetes
#18
Juan Pablo Frias, Edward J Bastyr, Louis Vignati, Matthias H Tschöp, Christophe Schmitt, Klara Owen, Rune Haubo Christensen, Richard D DiMarchi
Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28748377/microvascular-effects-of-glucagon-like-peptide-1-receptor-agonists-in-type-2-diabetes-a-meta-analysis-of-randomized-controlled-trials
#19
Ilaria Dicembrini, Besmir Nreu, Alessia Scatena, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci, Matteo Monami
AIMS: Results with GLP1-receptor agonists (GLP-1RA) on microvascular complications of diabetes are contrasting. In trials designed for cardiovascular outcomes, both liraglutide and semaglutide were associated with a relevant reduction in the incidence and progression of nephropathy. On the other hand, in the same trials, semaglutide was associated with an increased progression of retinopathy, and a similar trend was observed for liraglutide. This meta-analysis is aimed at assessing the effects of GLP-1RA on retinopathy and nephropathy...
October 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28744255/glycemic-and-metabolic-effects-of-two-long-bouts-of-moderate-intensity-exercise-in-men-with-normal-glucose-tolerance-or-type-2-diabetes
#20
Saeed Reza Eshghi, Kevin Fletcher, Étienne Myette-Côté, Cody Durrer, Raniah Q Gabr, Jonathan P Little, Peter Senior, Craig Steinback, Margie H Davenport, Gordon J Bell, Dion R Brocks, Normand G Boulé
BACKGROUND: The glycemic and insulinemic responses following 30-60 min of exercise have been extensively studied, and a dose-response has been proposed between exercise duration, or volume, and improvements in glucose tolerance or insulin sensitivity. However, few studies have examined the effects of longer bouts of exercise in type 2 diabetes (T2D). Longer bouts may have a greater potential to affect glucagon, interleukin-6 (IL-6) and incretin hormones [i.e., glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)]...
2017: Frontiers in Endocrinology
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