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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
July 12, 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
#8
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...
June 28, 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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
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
#15
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...
August 1, 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
#16
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
#17
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...
July 2017: 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
#18
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
#19
RANDOMIZED CONTROLLED TRIAL
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-inhibitor-of-dipeptidyl-peptidase-4-for-the-treatment-of-type-2-diabetes-mellitus
#20
Mukul R Jain, Amit A Joharapurkar, Samadhan G Kshirsagar, Vishal J Patel, Rajesh H Bahekar, Harilal V Patel, Pradip A Jadav, Pankaj R Patel, Ranjit C Desai
BACKGROUND AND PURPOSE: Dipeptidyl peptidase (DPP)-4 inhibitors increase levels of glucagon-like peptide-1 (GLP-1) and provide clinical benefit in the treatment of type 2 diabetes mellitus. As longer acting inhibitors have therapeutic advantages, 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, in vitro, with assays of DPP-4 activity...
July 2017: British Journal of Pharmacology
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