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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
#1
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
#2
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
#3
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)...
September 28, 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
#4
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...
September 25, 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
#5
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...
September 20, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28870887/appetite-food-intake-and-gut-hormone-responses-to-intense-aerobic-exercise-of-different-duration
#6
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/m(2); 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
#7
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
#8
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
#9
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
#10
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...
July 27, 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
#11
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
https://www.readbyqxmd.com/read/28704555/a-system-model-of-the-effects-of-exercise-on-plasma-interleukin-6-dynamics-in-healthy-individuals-role-of-skeletal-muscle-and-adipose-tissue
#12
Micaela Morettini, Maria Concetta Palumbo, Massimo Sacchetti, Filippo Castiglione, Claudia Mazzà
Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution...
2017: PloS One
https://www.readbyqxmd.com/read/28701300/duodenal-and-ileal-glucose-infusions-differentially-alter-gastrointestinal-peptides-appetite-response-and-food-intake-a-tube-feeding-study
#13
RANDOMIZED CONTROLLED TRIAL
Sally D Poppitt, Hyun Sang Shin, Anne-Thea McGill, Stephanie C Budgett, Kim Lo, Malcolm Pahl, Janice Duxfield, Mark Lane, John R Ingram
Background: Activation of the ileal brake through the delivery of nutrients into the distal small intestine to promote satiety and suppress food intake provides a new target for weight loss. Evidence is limited, with support from naso-ileal lipid infusion studies.Objective: The objective of the study was to investigate whether glucose infused into the duodenum and ileum differentially alters appetite response, food intake, and secretion of satiety-related gastrointestinal peptides.Design: Fourteen healthy male participants were randomly assigned to a blinded 4-treatment crossover, with each treatment of single-day duration...
September 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28657399/combination-sglt2-inhibitor-and-glp-1-receptor-agonist-therapy-a-complementary-approach-to-the-treatment-of-type-2-diabetes
#14
Robert S Busch, Michael P Kane
Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia...
September 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28647503/exogenous-glucagon-like-peptide-1-reduces-body-weight-and-cholecystokinin-8-enhances-this-reduction-in-diet-induced-obese-male-rats
#15
Thaer R Mhalhal, Martha C Washington, Kayla Newman, John C Heath, Ayman I Sayegh
The sites of action regulating meal size (MS) and intermeal interval (IMI) length by glucagon like peptide-1 (7-36) (GLP-1 (7-36)) and cholecystokinin-8 (CCK-8) reside in the areas supplied by the two major branches of the abdominal aorta, celiac and cranial mesenteric arteries. We hypothesized that infusing GLP-1 near those sites reduces body weight (BW) and adding CCK-8 to this infusion enhances the reduction. Here, we measured BW in diet-induced obese (DIO) male rats maintained and tested on normal rat chow and infused with saline, GLP-1 (0...
June 21, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28639755/-the-combination-of-glp-1-analogs-and-sglt2-inhibitors-new-perspectives
#16
Claire Ritz, Jaafar Jaafar, Jacques Philippe
Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28601988/surgical-and-advanced-medical-therapy-for-the-treatment-of-type-2-diabetes-in-class-i-obese-patients-a-short-term-outcome
#17
Mohit Bhandari, Winni Mathur, Ravindra Kumar, Arun Mishra, Mahak Bhandari
BACKGROUND: Bariatric surgery, incretin-based therapy (glucagon-like peptide-1 analogues), and sodium-glucose co-transporter 2 (SGLT2) inhibitors have antidiabetic properties in morbidly obese patients. However, their comparative efficacy in treating type 2 diabetes mellitus (T2DM) in class I obese patients specifically in Indian has not been studied yet. This study evaluates and compares the efficacy and side effect of surgical and advanced medical management of T2DM in class I obese patients...
June 11, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28569363/glucagon-like-peptide-1-receptor-agonists-and-atrial-fibrillation-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#18
M Monami, B Nreu, A Scatena, S Giannini, F Andreozzi, G Sesti, E Mannucci
BACKGROUND: The pharmacological stimulation of GLP-1 receptors is associated with an increase in heart rate. A pooled analysis of patient-level data from phase III trials with albiglutide revealed a significant increase in the risk of atrial fibrillation. Aim of the present meta-analysis is to summarize all available evidence on the effects of individual GLP-1 receptor agonists (RA), and of the whole class, on the incidence of atrial fibrillation. METHODS: A Medline search for GLP-1 RA (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥12 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 RA with placebo or any other non-GLP-1 RA drug...
May 31, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28565889/renal-function-markers-and-metformin-eligibility
#19
Carlos Tavares Bello, Ricardo Castro Fonseca, Francisco Sousa Santos, João Sequeira Duarte, Jorge Azinheira, Carlos Vasconcelos
BACKGROUND: Metformin is the cornerstone of the pharmacological therapy for type 2 Diabetes (T2D). It belongs to the biguanide class of drugs and it improves hepatic insulin resistance and enhances GLP-1 and peptide YY secretion. Although being considered safe regarding hypoglycemic risk, renal dysfunction remains the main obstacle to its use due to the underlying risk of lactic acidosis. In the recent past many authors used creatinine values as the decisive marker when it came to choose between pharmacological agents in DM...
May 31, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/28547565/an-optimized-ies-method-and-its-inhibitory-effects-and-mechanisms-on-food-intake-and-body-weight-in-diet-induced-obese-rats-ies-for-obesity
#20
Xinyue Wan, Jieyun Yin, Robert Foreman, Jiande D Z Chen
PURPOSE: This paper aims to optimize stimulation parameters and durations for intestinal electrical stimulation (IES) and to explore the effects and mechanisms of chronic IES with optimized methodology in obesity rats. MATERIALS AND METHODS: Sixteen diet-induced obese (DIO) rats were tested for food intake with four different sets of IES parameters each lasting 1 week. Then, another 12 DIO rats were used to test the effect of IES on food intake with different stimulation durations...
May 25, 2017: Obesity Surgery
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