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Dipeptidyl peptidase

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https://www.readbyqxmd.com/read/28211608/preclinical-characterisation-of-55p0251-a-novel-compound-that-amplifies-glucose-stimulated-insulin-secretion-and-counteracts-hyperglycaemia-in-rodents
#1
Karin Stadlbauer, Barbara Brunmair, Zsuzsanna Lehner, Immanuel Adorjan, Thomas Scherer, Anton Luger, Leonhardt Bauer, Clemens Fürnsinn
AIMS: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action. MATERIALS AND METHODS: Pharmacokinetic properties of 55P0251 were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets, and comparison to established drugs...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28211604/delays-in-treatment-intensification-with-oral-antidiabetic-drugs-and-risk-of-microvascular-and-macrovascular-events-in-patients-with-poor-glycemic-control-an-individual-patient-simulation-study
#2
Henry J Folse, Jayanti Mukherjee, John J Sheehan, Alexandra J Ward, Ryan L Pelkey, Tuan A Dinh, Lei Qin, Jennifer Kim
AIMS: Despite guideline recommendations, many patients with type 2 diabetes on oral antidiabetic drugs (OADs) whose HbA1c results remain above target do not experience timely treatment intensification. This study uses the Archimedes Model® to estimate the consequences of delays in OAD treatment intensification on glycemic control and long-term outcomes at 5 and 20 years. MATERIALS AND METHODS: Using real world data, we modeled a cohort of hypothetical patients with HbA1c ≥8%, on metformin, with no history of insulin use...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28205322/efficacy-and-safety-of-autoinjected-exenatide-once-weekly-suspension-versus-sitagliptin-or-placebo-with-metformin-in-patients-with-type-2-diabetes-the-duration-neo-2-randomized-clinical-study
#3
Kishore M Gadde, Marion L Vetter, Nayyar Iqbal, Elise Hardy, Peter Öhman
AIMS: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo. MATERIALS AND METHODS: In this open-label, multicenter study of patients with type 2 diabetes who had suboptimal glycemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28201967/dipeptidyl-peptidase-4-inhibitor-induced-angioedema-an-overlooked-and-potentially-lethal-adverse-drug-reaction
#4
Susanne Irene Scott, Michelle Fog Andersen, Lise Aagaard, Christian Von Buchwald, Eva Rye Rasmussen
Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. Dipeptidyl peptidase-4 inhibitors are anti-diabetic drugs used to improve glycaemic control. They, as a class effect, inadvertently affect the degradation of the vasoactive kinins bradykinin and substance P, both of which can cause angioedema due to vasodilatation and increase in vascular permeability in the capillaries...
February 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28197977/interpreting-cardiovascular-endpoints-in-trials-of-antihyperglycemic-drugs
#5
REVIEW
Himika Chawla, Nikhil Tandon
In view of the significant cardiovascular (CV) morbidity and mortality in patients with type 2 diabetes mellitus, and concerns raised about the CV safety of some glucose-lowering drugs, the US Food and Drug Administration (FDA) issued guidance for the industry in 2008 to demonstrate CV safety for the approval of all new antihyperglycemic drugs. Seven randomized controlled trials involving around 60,000 participants have been completed so far and have demonstrated the CV safety of dipeptidyl peptidase 4 inhibitors (saxagliptin, alogliptin and sitagliptin), glucagon-like peptide-1 receptor agonists (lixisenatide, liraglutide and semaglutide) and a sodium-glucose co-transporter 2 inhibitor (empagliflozin) in patients with type 2 diabetes...
February 14, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28195389/no-increased-risk-of-cardiovascular-events-in-older-adults-initiating-dipeptidyl-peptidase-4-inhibitors-versus-therapeutic-alternatives
#6
Mugdha Gokhale, John B Buse, Michele Jonsson Funk, Jennifer Lund, Virginia Pate, Ross J Simpson, Til Stürmer
OBJECTIVE: Randomized placebo-controlled trials have examined the cardiovascular (CV) effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), but data on incidence relative to therapeutic alternatives are limited in the older US Medicare population. We compared the CV risk with DPP-4i relative to sulfonylureas (SU) and thiazolidinediones (TZD). METHODS: During 2007-2013, using Medicare beneficiaries >65 years we identified two new-user cohorts without the use of drugs being compared in the 6 months before initiation: DPP-4i versus SU and DPP-4i versus TZD...
February 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28187861/corrigendum-to-demographic-and-clinical-characteristics-of-type-2-diabetes-mellitus-patients-initiating-dipeptidyl-peptidase-4-inhibitors-a-retrospective-study-of-uk-general-practice-clin-ther-2016-8-1825-1832-e15
#7
Abigail Tebboth, Sally Lee, Anna Scowcroft, Paula Bingham-Gardiner, William Spencer, John Bolodeoku, Syed Wasi Hassan
No abstract text is available yet for this article.
February 7, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28183314/dpp-4-inhibition-has-no-acute-effect-on-bnp-and-its-n-terminal-pro-hormone-measured-by-commercial-immune-assays-a-randomized-cross-over-trial-in-patients-with-type-2-diabetes
#8
Gian Paolo Fadini, Benedetta Maria Bonora, Mattia Albiero, Martina Zaninotto, Mario Plebani, Angelo Avogaro
BACKGROUND: Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD)...
February 10, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28182722/hemoglobin-glycation-index-as-a-useful-predictor-of-therapeutic-responses-to-dipeptidyl-peptidase-4-inhibitors-in-patients-with-type-2-diabetes
#9
Yu-Wei Chen, Jun-Sing Wang, Wayne H-H Sheu, Shih-Yi Lin, I-Te Lee, Yuh-Min Song, Chia-Po Fu, Chia-Lin Lee
INTRODUCTION: A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. METHODS: This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level...
2017: PloS One
https://www.readbyqxmd.com/read/28180064/dipeptidyl-peptidase-4-inhibitor-treatment-induces-a-greater-increase-in-plasma-levels-of-bioactive-gip-than-glp-1-in-non-diabetic-subjects
#10
Tsuyoshi Yanagimachi, Yukihiro Fujita, Yasutaka Takeda, Jun Honjo, Hidemitsu Sakagami, Hiroya Kitsunai, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Timothy J Kieffer, Masakazu Haneda
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) possess multiple bioactive isoforms that are rendered non-insulinotropic by the enzyme dipeptidyl peptidase-4 (DPP-4). Recently, some ELISA kits have been developed to specifically measure "active" GIP and GLP-1, but it is unclear if these kits can accurately quantify all bioactive forms. Therefore, it remains uncertain to what extent treatment with a DPP-4 inhibitor boosts levels of biologically active GIP and GLP-1...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28179397/dipeptidyl-peptidase-4-induces-aortic-valve-calcification-by-inhibiting-insulin-like-growth-factor-1-signaling-in-valvular-interstitial-cells
#11
Bongkun Choi, Sahmin Lee, Sang-Min Kim, Eun-Jin Lee, Sun Ro Lee, Dae-Hee Kim, Jeong Yoon Jang, Sang-Wook Kang, Ki-Up Lee, Eun-Ju Chang, Jae-Kwan Song
Background -Calcification of the aortic valve leads to increased leaflet stiffness, and consequently to the development of calcific aortic valve disease (CAVD); however, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes CAVD progression. Methods -We obtained the aortic valve tissues from humans and murine models (wild type and eNOS(-/-) mice), and cultured the valvular interstitial cells (VICs) and valvular endothelial cells (VECs) from the cusps...
February 8, 2017: Circulation
https://www.readbyqxmd.com/read/28178698/dipeptidyl-peptidase-4-inhibitors-in-chronic-kidney-disease-a-systematic-review-of-randomized-clinical-trials
#12
Simon R Walker, Paul Komenda, Suhail Khojah, Wafa Al-Tuwaijri, Kerry MacDonald, Brett Hiebert, Neil Tangri, Stewart W D Nadurak, Thomas W Ferguson, Claudio Rigatto, Navdeep Tangri
BACKGROUND: Chronic kidney disease (CKD) is common in patients with type 2 diabetes mellitus (T2DM) and limits therapeutic options. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a novel class of oral glucose-lowering agents and are known to be safe and effective in the general population. METHODS: We searched Cochrane, EMBASE, and PubMed from the time of their inception until March 2015. We included randomized controlled trials analyzing the efficacy (change in hemoglobin A1C [HbA1C]) and safety of DPP-4 agents in individuals with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1...
February 9, 2017: Nephron
https://www.readbyqxmd.com/read/28177527/effects-of-linagliptin-on-human-immortalized-podocytes-a-cellular-system-to-study-dipeptidyl-peptidase-4-inhibition
#13
Gianluca Miglio, Giovanna Vitarelli, Thomas Klein, Elisa Benetti
BACKGROUND AND PURPOSE: Dipeptidyl-peptidase (DPP)4 is expressed by resident renal cells, including glomerular cells. Dipeptidyl-peptidase 4 inhibitors (gliptins) exert albuminuria lowering effects, but the role of renal DPP4 as a pharmacological target has not been elucidated. To better understand the actions of gliptins, the effects of linagliptin on behaviour of immortalized human podocytes and mesangial cells have been evaluated. EXPERIMENTAL APPROACH: Expression of DPP4 was measured at both the mRNA and protein levels...
February 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28177187/efficacy-and-safety-of-canagliflozin-as-add-on-therapy-to-teneligliptin-in-japanese-patients-with-type-2-diabetes-mellitus-results-of-a-24-week-randomised-double-blind-placebo-controlled-trial
#14
Takashi Kadowaki, Nobuya Inagaki, Kazuoki Kondo, Kenichi Nishimura, Genki Kaneko, Nobuko Maruyama, Nobuhiro Nakanishi, Hiroaki Iijima, Yumi Watanabe, Maki Gouda
AIMS: To investigate efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin administered as add-on therapy to the dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial in Japanese patients with T2DM who had inadequate glycaemic control with teneligliptin. Patients were randomised to receive teneligliptin 20 mg plus either canagliflozin 100 mg (T + C, n = 70) or placebo (T + P, n = 68) once daily...
February 8, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28177092/-newer-anti-diabetic-therapies-and-chronic-kidney-disease
#15
Luca Di Lullo, Claudio Ronco, Vincenzo Barbera, Mario Cozzolino, Francesca Santoboni, Annalisa Villani, Antonio De Pascalis, Antonio Bellasi
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), whose most common causes include hypertension, arteriosclerosis, and diabetes. About 40% of patients with diabetes develop CKD. Intensive blood glucose control through pharmacological intervention can delay CKD progression. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 25) and without dose adjustment...
January 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28176959/a-systematic-literature-review-on-the-efficacy-effectiveness-gap-comparison-of-randomized-controlled-trials-and-observational-studies-of-glucose-lowering-drugs
#16
REVIEW
Mikkel Z Ankarfeldt, Erpur Adalsteinsson, Rolf Hh Groenwold, M Sanni Ali, Olaf H Klungel
AIM: To identify a potential efficacy-effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. METHODS: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176886/assessment-of-channeling-bias-among-initiators-of-glucose-lowering-drugs-a-uk-cohort-study
#17
Mikkel Z Ankarfeldt, Brian L Thorsted, Rolf Hh Groenwold, Erpur Adalsteinsson, M Sanni Ali, Olaf H Klungel
BACKGROUND: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding). AIM: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea. METHODS: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176222/saxagliptin-dapagliflozin-a-review-in-type-2-diabetes-mellitus
#18
Karly P Garnock-Jones
Saxagliptin/dapagliflozin fixed-dose combination tablets (Qtern(®)) are indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus (T2DM), either when treatment with metformin and/or a sulfonylurea plus a monocomponent of saxagliptin/dapagliflozin provides inadequate glycaemic control, or when the patient is already being treated with the free combination of saxagliptin + dapagliflozin. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the use of saxagliptin/dapagliflozin in this indication...
February 7, 2017: Drugs
https://www.readbyqxmd.com/read/28175014/p198-dipeptidyl-peptidase-4-a-strong-predictive-marker-of-disease-activity-and-treatment-escalation-in-inflammatory-bowel-diseases
#19
P Pinto-Lopes, J Afonso, G Macedo, F Magro
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28169131/association-of-dipeptidyl-peptidase-4-inhibitors-with-risk-of-metastases-in-patients-with-type-2-diabetes-and-breast-prostate-or-digestive-system-cancer
#20
Wolfgang Rathmann, Karel Kostev
AIMS: Experimental and animal studies have supported the hypothesis that dipeptidyl peptidase-4 inhibitors (DPP-4i) may accelerate tumor metastasis. The aim was to analyze the relationships between DPP-4i therapy with risk of metastases in type 2 diabetes patients with breast, prostate and digestive organ cancers. METHODS: Type 2 diabetes patients with first diagnoses of breast, prostate or digestive organ cancer were selected in general and internal medicine practices (Disease Analyzer Germany: 01/2008-12/2014)...
January 26, 2017: Journal of Diabetes and its Complications
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