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https://www.readbyqxmd.com/read/28967594/rationale-and-design-of-the-darwin-t2d-dapagliflozin-real-world-evidence-in-type-2-diabetes-a-multicenter-retrospective-nationwide-italian-study-and-crowdsourcing-opportunity
#1
G P Fadini, G Zatti, A Consoli, E Bonora, G Sesti, A Avogaro
BACKGROUND: Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. AIMS: We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society...
August 8, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28956360/effects-of-incretin-based-therapies-on-diabetic-microvascular-complications
#2
REVIEW
Yu Mi Kang, Chang Hee Jung
The morbidity and mortality associated with diabetic complications impose a huge socioeconomic burden worldwide. Therefore, the ultimate goal of managing diabetes mellitus (DM) is to lower the risk of macrovascular complications and highly morbid microvascular complications such as diabetic nephropathy (DN) and diabetic retinopathy (DR). Potential benefits of incretin-based therapies such as glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on the diabetic macrovascular complications have been recently suggested, owing to their pleiotropic effects on multiple organ systems...
September 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28950045/non-st-elevation-myocardial-infarction-nstemi-outcome-in-type-2-diabetic-patients-with-non-obstructive-coronary-artery-stenosis-effects-of-incretin-treatment
#3
Raffaele Marfella, Celestino Sardu, Paolo Calabrò, Mario Siniscalchi, Fabio Minicucci, Giuseppe Signoriello, Maria Luisa Balestrieri, Ciro Mauro, Maria Rosaria Rizzo, Giuseppe Paolisso, Michelangela Barbieri
No proper data on prognosis and management of type-2 diabetic patients with non-obstructive coronary artery stenosis (NOCS)-Non-ST-Elevation Myocardial Infarction (NSTEMI) exist. We evaluated the 12-months prognosis of NOCS-diabetics (20-49% luminal stenosis) with first NSTEMI as compared with non-diabetics. Moreover, we investigated the 12-months prognosis in NSTEMI-NOCS diabetics, previously treated with incretin-based therapy, compared with a matched cohort of NSTEMI-NOCS never treated with such therapy...
September 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28943949/sitagliptin-a-dipeptidyl-peptidase-4-inhibitor-suppresses-cxcl5-and-sdf-1-and-does-not-accelerate-intestinal-neoplasia-formation-in-apc-min-mice-fed-a-high-fat-diet
#4
Kaori Fujiwara, Takuya Inoue, Yujiro Henmi, Yoshimasa Hirata, Yutaka Naka, Azusa Hara, Kazuki Kakimoto, Sadaharu Nouda, Toshihiko Okada, Ken Kawakami, Toshihisa Takeuchi, Kazuhide Higuchi
The relationship between type 2 diabetes mellitus and intestinal neoplasia has been shown epidemiologically. A high-fat diet (HFD) is also known to promote insulin resistance, which is a risk factor for intestinal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in the clinic for the treatment of type 2 diabetes and also to prolong the effects of glucagon-like peptide-1 (GLP-1). However, since the intestinotrophic hormone GLP-2 and chemokines, such as CXCL5 and stromal cell-derived factor-1 (SDF-1), are also substrates of DPP-4, DPP-4 inhibitors may increase the risk of intestinal carcinogenesis...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#5
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28903385/dpp-4-enzyme-deficiency-protects-kidney-from-acute-ischemia-reperfusion-injury-role-for-remote-intermittent-bowel-ischemia-reperfusion-preconditioning
#6
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4(D)) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4(D)) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4(D), (3) KIR-F344 (4) KIR-DPP4(D), (5) DPP4(D)-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4(D) rats 72 h after acute KIR...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#7
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#8
REVIEW
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28879786/pharmacological-management-of-type-2-diabetes-what-s-new-in-2017
#9
André J Scheen
Introduction Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas covered Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients...
September 7, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28873383/incretins-and-their-endocrine-and-metabolic-functions
#10
Jochen Seufert
Incretins are hormones secreted into the blood stream from the gut mucosa in response to nutrient intake. They have been characterized based on their capacity to lower blood glucose levels. The more potent reduction of blood glucose coupled to a more intensive stimulation of insulin secretion, in response to oral glucose uptake, as compared to intravenous glucose infusion has further been termed the "incretin effect." As a prototype incretin hormone, the biology of glucagon-like peptide 1 (GLP-1) has been intensively studied...
2017: Endocrine Development
https://www.readbyqxmd.com/read/28869249/glp-1-and-the-kidney-from-physiology-to-pharmacology-and-outcomes-in-diabetes
#11
REVIEW
Marcel H A Muskiet, Lennart Tonneijck, Mark M Smits, Michaël J B van Baar, Mark H H Kramer, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
The gastrointestinal tract - the largest endocrine network in human physiology - orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects...
October 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28866826/impact-of-pioglitazone-regulatory-withdrawal-on-antidiabetic-drug-use-and-health-in-diabetic-patients
#12
Antoine Pariente, Yohann Mansiaux, Ana Jarné, Francesco Salvo, Cécile Pageot, Julien Bezin, Andy Smith, Bernard Bégaud
PURPOSE: In 2011, pioglitazone was withdrawn from the French market owing to a potential risk of bladder cancer. This study aimed at assessing the impact of this pioglitazone withdrawal (PW) considering (i) trends in antidiabetic uses and (ii) changes in hospitalization/death rates in diabetic patients following PW. METHODS: We first considered the general population of the Echantillon Généraliste des Bénéficiaires (EGB), a 1/97th representative sample of the French healthcare insurance system beneficiaries, for the 2010-2014 period...
September 2, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#13
Yanqing Zhang, Meifen Wu, Wynn Htun, Emily W Dong, Franck Mauvais-Jarvis, Vivian A Fonseca, Hongju Wu
Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#14
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28761216/use-of-canagliflozin-in-combination-with-and-compared-to-incretin-based-therapies-in-type-2-diabetes
#15
Richard E Pratley, Eugenio Cersosimo
In Brief Sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies (dipeptidyl peptidase-4 [DPP-4] inhibitors and glucagon-like peptide-1 [GLP-1] receptor agonists) are widely used to treat patients with type 2 diabetes. In clinical and real-world studies, canagliflozin, an SGLT2 inhibitor, has demonstrated superior A1C lowering compared to the DPP-4 inhibitor sitagliptin. Canagliflozin can also promote modest weight/fat loss and blood pressure reduction. The addition of canagliflozin to treatment regimens that include a DPP-4 inhibitor or a GLP-1 receptor agonist has been shown to further improve glycemic control, while still maintaining beneficial effects on cardiometabolic parameters such as body weight and blood pressure...
July 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/28750074/dpp4-gene-variation-affects-glp-1-secretion-insulin-secretion-and-glucose-tolerance-in-humans-with-high-body-adiposity
#16
Anja Böhm, Robert Wagner, Fausto Machicao, Jens Juul Holst, Baptist Gallwitz, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger
OBJECTIVE: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type-2 diabetes (TÜF)...
2017: PloS One
https://www.readbyqxmd.com/read/28746743/the-incretin-concept-revised-the-origin-of-glp-1-s-insulinotropic-function-the-gut-the-islets-or-both
#17
Daisuke Yabe, Yusuke Seino, Yutaka Seino
Incretins comprise a pair of gut hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which are secreted in response to food ingestion and enhance glucose-dependent insulin secretion (GIIS) from pancreatic β-cells. Immediately after secretion, GLP-1 is degraded by dipeptidyl peptidase-4 (DPP-4) more rapidly than GIP, and circulating levels of biologically intact GLP-1 are substantially lower than those of biologically intact GIP. Therefore, there has been a debate on how the gut-derived GLP-1 exerts insulinotropic actions...
July 26, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28743778/fracture-risk-associated-with-common-medications-used-in-treating-type-2-diabetes-mellitus
#18
Daniel Wolverton, Melissa M Blair
PURPOSE: Published data on the risk of bone fractures associated with medications used for the treatment of type 2 diabetes mellitus are summarized. SUMMARY: A systematic literature search identified 108 publications on controlled trials and 6 meta-analyses addressing the potential for fractures with the use of 7 commonly used antidiabetic classes: thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, biguanides, insulin, and sulfonylureas...
August 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28741456/effects-of-oral-and-non-insulin-injectable-antidiabetic-treatment-in-hypertension-a-systematic-review
#19
Vasiliki Katsi, Georgios Georgiopoulos, Georgia Vogiatzi, Dimitrios Oikonomou, Maria Megapanou, John Skoumas, Charalampos Vlachopoulos, Petros Nihoyannopoulos, Dimitris Tousoulis
BACKGROUND: Diabetes mellitus type 2 (T2DM) often co-exists with hypertension, and this aggregation of co-morbidities amplifies the risk for future cardiovascular events. Therefore, it appears crucial to understand the essence of choosing oral and non-insulin injectable anti-diabetic drugs (ADs) with a favorable hemodynamic impact that could partially attenuate the increased baseline cardiovascular risk. OBJECTIVE: We sought to evaluate the effect of ADs on blood pressure (BP) indices and to assess the potential role of certain ADs towards hypertension treatment...
May 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28725624/incretin-effect-of-urena-lobata-leaves-extract-on-structure-and-function-of-rats-islet-%C3%AE-cells
#20
Y Purnomo, D W Soeatmadji, S B Sumitro, M A Widodo
This study aims to determine the incretin effects of Urena lobata leaves extract on the structure and function of rats islet β-cells. This study utilizes male Sprague-Dawley rats divided into 2 control group and 3 test group (n = 5). Diabetic rats were induced with High Fructose Diet (HFD) and single dose intraperitoneal streptozotocin 25 mg/kg bw. Aqueous leaves extract of U. lobata was prepared by decoction methods and administrated orally with doses of 250, 500, and 1000 mg/kg bw for 4 weeks then incretin effect was evaluated by measuring serum GLP-1, insulin, and blood glucose levels...
July 2017: Journal of Traditional and Complementary Medicine
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