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https://www.readbyqxmd.com/read/29677303/association-between-use-of-sodium-glucose-cotransporter-2-inhibitors-glucagon-like-peptide-1-agonists-and-dipeptidyl-peptidase-4-inhibitors-with-all-cause-mortality-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#1
Sean L Zheng, Alistair J Roddick, Rochan Aghar-Jaffar, Matthew J Shun-Shin, Darrel Francis, Nick Oliver, Karim Meeran
Importance: The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown. Objective: To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis. Data Sources: MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017...
April 17, 2018: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29675798/a-systematic-literature-review-and-network-meta-analysis-comparing-once-weekly-semaglutide-with-other-glp-1-receptor-agonists-in-patients-with-type-2-diabetes-previously-receiving-1-2-oral-anti-diabetic-drugs
#2
Michal Witkowski, Lars Wilkinson, Neil Webb, Alan Weids, Divina Glah, Hrvoje Vrazic
INTRODUCTION: Once-weekly semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue administered at a 1.0 or 0.5 mg dose. As head-to-head trials assessing once-weekly semaglutide as an add-on to 1-2 oral anti-diabetic drugs (OADs) vs other GLP-1 receptor agonists (GLP-1 RAs) are limited, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of once-weekly semaglutide vs GLP-1 RAs in patients with type 2 diabetes (T2D) inadequately controlled on 1-2 OADs...
April 19, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29675797/treatment-intensification-in-type-2-diabetes-a-real-world-study-of-2-oad-regimens-glp-1-ras-or-basal-insulin
#3
Lawrence Blonde, Denis Raccah, Elisheva Lew, Juliana Meyers, Elena Nikonova, Mayank Ajmera, Keith L Davis, Monica Bertolini, Bruno Guerci
INTRODUCTION: Treatment guidelines recommend a stepwise approach to glycemia management in patients with type 2 diabetes (T2D), but this may result in uncontrolled glycated hemoglobin A1c (HbA1c) between steps. This retrospective analysis compared clinical and economic outcomes among patients with uncontrolled T2D initiating two oral antidiabetes drugs (OADs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or basal insulin in a real-world setting. METHODS: Adults with T2D on OAD monotherapy were identified in the MarketScan claims database (2007-2014)...
April 19, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29674332/potent-sglt1-2-dual-inhibition-improves-glycemic-control-without-marked-gastrointestinal-adaptation-or-colonic-microbiota-changes-in-rodents
#4
Fuyong Du, Simon Hinke, Cassandre Cavanaugh, David Polidori, Nathanial Wallace, Thomas Kirchner, Matthew Jennis, Wensheng Lang, Gee-Hong Kuo, Micheal Gaul, James Lenhard, Keith Demarest, Nadim J Ajami, Yin Liang, Pamela J Hornby
The sodium/glucose cotransporters (SGLT1 and SGLT2) transport glucose across the intestinal brush border and kidney tubule. Dual SGLT1/2 inhibition could reduce hyperglycemia more than SGLT2-selective in patients with Type 2 Diabetes; however, questions remain about altered gastrointestinal (GI) luminal glucose and tolerability. Therefore, this was evaluated in slc5a1-/- mice or using a potent dual inhibitor (cmpd 8; SGLT1 Ki = 1.5±0.5nM 100 fold > potency than phlorizin; SGLT2 Ki = 0.4±0.2 nM). 13C6-glucose uptake was quantified in slc5a1 -/- mice and in isolated rat jejunum...
April 19, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29673717/novel-fatty-acid-chain-modified-glp-1-derivatives-with-prolonged-in-vivo-glucose-lowering-ability-and-balanced-glucoregulatory-activity
#5
Xingguang Cai, Lidan Sun, Yuxuan Dai, Yosefa Avraham, Chunxia Liu, Jing Han, Yuan Liu, Dazhi Feng, Wenlong Huang, Hai Qian
Glucagon-like peptide-1 is a potent hypoglycemic hormone with beneficial properties for the treatment of diabetes. However, its half-life is short because the rapid metabolic degradation. This study aims to prolong the half-life of glucagon-like peptide-1 through conjugation with the fatty acid side chain which helps the conjugates to interact with the albumin. Firstly, we chose two optimized polypeptide chains which have tremendous hypoglycemic effect named Cys17 -Gly8 -GLP-1(7-36)-NH2 and Cys37 -Gly8 -GLP-1(7-37)-NH2 , and various fatty acid chains were modified...
April 11, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29672742/older-subjects-with-%C3%AE-cell-dysfunction-have-an-accentuated-incretin-release
#6
José de Jesús Garduno-Garcia, Amalia Gastaldelli, Ralph A DeFronzo, Raweewan Lertwattanarak, Jens J Holst, Nicolas Musi
Objective: Insulin secretion declines with age and this contributes to the increased risk of developing impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older subjects. Insulin secretion is regulated by the incretin hormones glucagon-like peptide (GLP) 1 and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is reduced in older subjects, and that this decline is associated with β-cell dysfunction. Research Design: 40 young (25±3 y) and 53 older (74±7 y) lean non-diabetic subjects underwent a 2 h oral glucose tolerance test (OGTT)...
April 16, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29672196/the-effects-of-synbiotic-supplementation-on-body-mass-index-metabolic-and-inflammatory-biomarkers-and-appetite-in-patients-with-metabolic-syndrome-a-triple-blind-randomized-controlled-trial
#7
Samira Rabiei, Mehdi Hedayati, Bahram Rashidkhani, Navid Saadat, Rahebeh Shakerhossini
It has been shown recently that metabolic syndrome is associated with gut dysbiosis. The gut microbiota may be the main target for prevention or treatment of metabolic syndrome. We investigated the effects of synbiotic supplementation on metabolic syndrome. In this triple-blinded clinical trial, 46 Iranian patients with metabolic syndrome, from both sexes, aged 25-70 years, who fulfilled inclusion criteria were randomly categorized to receive either the synbiotic or a placebo capsule, twice a day for three months, plus a weight-loss diet using stratified random sampling based on body mass index (BMI)...
April 19, 2018: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/29671912/a-surface-plasmon-resonance-assay-for-characterisation-and-epitope-mapping-of-anti-glp-1-antibodies
#8
Lasse Thomsen, Leonid Gurevich
The incretin hormone glucagon-like peptide-1 (GLP-1) has been subject to substantial pharmaceutical research regarding the treatment of type 2 diabetes mellitus. However, quantification of GLP-1 levels remains complicated due to the low circulation concentration and concurrent existence of numerous metabolites, homologous peptides, and potentially introduced GLP-1 receptor agonists. Surface plasmon resonance (SPR) facilitates real-time monitoring allowing a more detailed characterisation of the interaction compared with conventional enzyme-linked immunosorbent assays (ELISA)...
April 19, 2018: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29671556/dpp-4-inhibitors-and-glp-1-receptor-agonists-for-prevention-or-delay-of-type-2-diabetes-mellitus-and-associated-complications
#9
Dustin K Smith, Matthew J Wessner
No abstract text is available yet for this article.
April 1, 2018: American Family Physician
https://www.readbyqxmd.com/read/29671019/lixisenatide-a-novel-glp-1-analog-protects-against-cerebral-ischemia-reperfusion-injury-in-diabetic-rats
#10
Rania G Abdel-Latif, Gehan H Heeba, Ashraf Taye, Mohamed M A Khalifa
Type 2 diabetes mellitus (T2DM) is a major risk factor for ischemic stroke accompanied by vascular dysfunction and poor cerebrovascular outcome. Lixisenatide is a glucagon like peptide-1 (GLP-1) analog that is recently used for T2DM treatment with established neuroprotective properties. This study investigated and compared the neuroprotective effect of lixisenatide against glimepiride on diabetic rats subjected to global cerebral ischemia/reperfusion (I/R) injury. T2DM-induced adult male Wistar rats were administered lixisenatide or glimepiride prior to induction of global cerebral I/R-induced injury...
April 18, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29670912/the-effects-of-sleeve-gastrectomy-on-glucose-metabolism-and-glucagon-like-peptide-1-in-goto-kakizaki-rats
#11
Laiyuan Li, Xiaolin Wang, Liangliang Bai, Huichuan Yu, Zenghong Huang, Anpei Huang, Yanxin Luo, Jianping Wang
Purpose: To investigate the effects of sleeve gastrectomy (SG) on glucose metabolism and changes in glucagon-like peptide 1 (GLP-1) in Goto-Kakizaki (GK) rats. Methods: GK rats were randomly assigned to one of three groups: SG, SG pair-fed plus sham surgery (PF-sham), and ad libitum-fed no surgery (control). Food intake, body weight, blood glucose, GLP-1 and insulin levels, and GLP-1 expression in the jejunum and ileum were compared. Results: The SG rats exhibited lower postoperative food intake, body weight, and fasting glucose than did the control rats ( P < 0...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29670680/gengnianchun-extends-the-lifespan-of-caenorhabditis-elegans-via-the-insulin-igf-1-signalling-pathway
#12
Fanhui Meng, Jun Li, Yanqiu Rao, Wenjun Wang, Yan Fu
Gengnianchun (GNC), a traditional Chinese medicine (TCM), is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against A β -induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans . However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29668601/efficacy-and-safety-of-once-weekly-semaglutide-for-the-treatment-of-type-2-diabetes-protocol-for-a-systematic-review-and-meta-analysis
#13
Fang-Hong Shi, Hao Li, Min Cui, Zai-Li Zhang, Zhi-Chun Gu, Xiao-Yan Liu
BACKGROUND: It is a great challenge for type 2 diabetes mellitus (T2DM) patients to maintain optimal glycemia, control body weight, blood pressure, and avoiding hypoglycemia. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) can stimulate glucose-dependent insulin while inhibit glucagon secretion, delay gastric emptying, reduce appetite, and energy intake. Recently, a new once-weekly GLP-1 RAs, semaglutide, has been registered to treat patients with T2DM. METHODS: We will search Medline, Embase, Cochrane Library, and the ClinicalTrials...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29667921/glycemic-control-of-type-2-diabetes-mellitus-across-stages-of-renal-impairment-information-for-primary-care-providers
#14
Lili Tong, Sharon Adler
Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and elevates individuals' risk for cardiovascular disease, the leading cause of morbidity and mortality in T2DM. Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications...
April 18, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29667023/liraglutide-effects-on-upper-gastrointestinal-investigations-implications-prior-to-bariatric-surgery
#15
Renuca Modi, Peter Rye, Sarah Cawsey, Daniel W Birch, Arya M Sharma
Liraglutide is a glucagon-like peptide type 1 (GLP-1) analogue that is approved for long-term obesity management in North America. While bariatric surgery remains the gold standard for weight loss, an increasing number of patients are on liraglutide in the setting of ongoing workup for bariatric surgery. The presence of gastrointestinal symptoms prior to bariatric surgery may prompt testing for dysmotility, which affects surgical decision making. Here we report six cases where treatment with liraglutide was associated with reversible reduction in gastric and esophageal motility in screening for bariatric surgery...
April 17, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29665351/neuroendocrine-response-to-gaba-b-receptor-agonism-in-alcohol-dependent-individuals-results-from-a-combined-outpatient-and-human-laboratory-experiment
#16
Mehdi Farokhnia, Mikela B Sheskier, Mary R Lee, April N Le, Erick Singley, Sofia Bouhlal, Timmy Ton, Zhen Zhao, Lorenzo Leggio
Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the nervous system, plays an important role in biobehavioral processes that regulate alcohol seeking, food intake, and stress response. The metabotropic GABA-B receptor has been investigated as a potential therapeutic target for alcohol use disorder, by using orthosteric agonists (e.g., baclofen) and positive allosteric modulators. Whether and how pharmacological manipulation of the GABA-B receptor, in combination with alcohol intake, may affect feeding- and stress-related neuroendocrine pathways remains unknown...
April 14, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29663628/exenatide-effects-on-gastric-emptying-and-oral-glucose-appearance-in-plasma-a-quantitative-assessment-using-an-integrative-systems-pharmacology-model
#17
Veronika Voronova, Kirill Zhudenkov, Robert C Penland, David W Boulton, Gabriel Helmlinger, Kirill Peskov
Glucagon-like peptide (GLP)-1 and synthetic GLP-1 receptor agonists (GLP-1RA) slow gastric emptying rate (GER), thereby decreasing the Glucose Rate of Appearance (GluRA) in plasma, which may contribute to postprandial plasma glucose (PPG) stabilization under GLP-1RA treatment. A quantitative systems pharmacology (QSP) approach was used to evaluate the effect of exenatide immediate release (IR), a short-acting GLP-1RA, on GER and GluRA. The proposed model is based on the data from multiple published sources including: (1) GLP-1 and exenatide plasma concentration-time profiles; (2) GER estimates under placebo, GLP-1 or exenatide IR dosing; (3) GluRA measurements upon food intake...
April 16, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29660230/the-use-of-antimicrobials-as-adjuvant-therapy-for-the-treatment-of-obesity-and-insulin-resistance-effects-and-associated-mechanisms
#18
REVIEW
Sandra Aparecida Dos Reis, Maria do Carmo Gouveia Peluzio, Josefina Bressan
The intestinal microbiota has come to be considered an additional risk factor for the development of metabolic diseases. Considering the potential role of antimicrobials as modulators of the intestinal microbiota, they have been investigated for use in the adjuvant treatment of obesity and insulin resistance. In this regard, the present manuscript aimed to review the effect of regular use of antimicrobials on the treatment of obesity and/or IR, as well as its associated mechanisms. The regular use of antimicrobials does not seem to influence the body weight and adiposity of its consumer...
April 16, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29659867/gastric-emptying-impacts-the-timing-of-meal-glucose-peak-on-subjects-with-uncomplicated-type-1-diabetes
#19
Roberta Lupoli, Annalisa Creanza, Ettore Griffo, Gerardo Nardone, Alba Rocco, Lutgarda Bozzetto, Giovanni Annuzzi, Gabriele Riccardi, Brunella Capaldo
Context: Diabetes mellitus (DM) is associated with gastrointestinal (GI) motility dysfunction, ranging from delayed to accelerated gastric emptying (GE). Objective: To evaluate GE in type 1 DM (T1DM) patients without chronic complications and to investigate its relation with postprandial glucose and GI hormones responses. Design: Cross-sectional study. Setting/Participants: Forty-two T1DM patients free of chronic complications referred to "Federico II" University and 31 healthy controls comparable for age, gender and BMI...
April 11, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29659121/glucagon-like-peptide-1-ameliorates-cardiac-lipotoxicity-in-diabetic-cardiomyopathy-via-the-ppar%C3%AE-pathway
#20
Lujin Wu, Ke Wang, Wei Wang, Zheng Wen, Peihua Wang, Lei Liu, Dao Wen Wang
Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4 and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high-fat diets were significantly reversed by exendin-4 and saxagliptin treatments for 8 weeks...
April 16, 2018: Aging Cell
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