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Dpp 4 inhibitors

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https://www.readbyqxmd.com/read/28432754/intraclass-differences-in-the-risk-of-hospitalisazion-for-heart-failure-among-type-2-diabetic-patients-initiating-a-dipeptydil-peptidase-4-inhibitor-or-a-sulphonylurea-results-from-the-osmed-health-db-registry
#1
Gian Paolo Fadini, Stefania Saragoni, Pierluigi Russo, Luca Degli Esposti, Saula Vigili de Kreutzenberg, Mario Melazzini, Angelo Avogaro
AIMS: Heart failure (HF) is frequent in type 2 diabetes (T2D) and several glucose-lowering medications may increase HF risk. In the SAVOR-TIMI trial, patients on Saxagliptin experienced a 27% higher risk of hospitalisation for HF (HHF). In a retrospective study on 127,555 patients, we showed that DPP-4i therapy was associated with a lower HHF risk than sulphonylurea (SU) therapy. We herein re-analyzed such data to evaluate intraclass differences among DPP-4i and SU. MATERIALS AND METHODS: We included T2D patients initiating DPP-4i or SU alone or in combination with metformin...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#2
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28431666/glp-1-receptor-agonists-and-heart-failure-in-diabetes
#3
André J Scheen
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28420715/role-of-soluble-and-membrane-bound-dipeptidylpeptidase-4-in-diabetic-nephropathy
#4
Ahmed A Hasan, Berthold Hocher
Diabetic nephropathy is one of the most frequent, devastating, and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might have in addition reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians...
April 18, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28420649/a-sandwich-elisa-for-measurement-of-the-primary-glucagon-like-peptide-1-metabolite
#5
Nicolai J Wewer Albrechtsen, Ali Asmar, Frederik Jensen, Signe Törang, Lene Simonsen, Rune E Kuhre, Meena Asmar, Simon Veedfald, Astrid Plamboeck, Filip K Knop, Tina Vilsboll, Sten Madsbad, Michael A Nauck, Carolyn F Deacon, Jens Bulow, Jens J Holst, Bolette Hartmann
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract. It is best known for its glucose-dependent insulinotropic effects GLP-1 is secreted in its intact (active) form (7-36NH2) but is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the primary metabolite (9-36NH2) before reaching the targets via the circulation. Although originally thought to be inactive or antagonistic, GLP-1 9-36NH2 may have independent actions, and it is therefore relevant to be able to measure it...
April 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28418262/adherence-and-persistence-in-patients-with-type-2-diabetes-mellitus-newly-initiating-canagliflozin-dapagliflozin-dpp-4s-or-glp-1s-in-the-united-states
#6
Jennifer Cai, Victoria Divino, Chakkarin Burudpakdee
OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors were first approved in the US in 2013; therefore, real-world (RW) studies describing outcomes are limited. This retrospective study evaluated adherence and persistence among patients initiating canagliflozin (CANA), dapagliflozin (DAPA), GLP-1 agonists (GLP-1s) and DPP-4 inhibitors (DPP-4s) over a 12-month follow-up from a US managed care perspective. METHODS: Patients newly initiating CANA, DAPA, GLP-1s, or DPP-4s from 2/1/2014-6/30/2014 were identified from the QuintilesIMS PharMetrics Plus Database...
April 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28408925/combination-therapy-with-a-sodium-glucose-cotransporter-2-inhibitor-and-a-dipeptidyl-peptidase-4-inhibitor-additively-suppresses-macrophage-foam-cell-formation-and-atherosclerosis-in-diabetic-mice
#7
Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Hideki Kushima, Makoto Ohara, Takuya Watanabe, Olov Andersson, Tsutomu Hirano
Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe(-/-) ) mice...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28408838/dpp-4-inhibitor-treatment-%C3%AE-cell-response-but-not-hba1c-reduction-is-dependent-on-the-duration-of-diabetes
#8
Plamen Kozlovski, Vaishali Bhosekar, James E Foley
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by enhancing insulin and suppressing glucagon secretion. Since T2DM is associated with progressive loss of β-cell function, we hypothesized that the DPP-4 inhibitor action to improve β-cell function would be attenuated with longer duration of T2DM. METHODS: Data from six randomized, placebo-controlled trials of 24 weeks duration, where β-cell response to vildagliptin 50 mg twice daily was assessed, were pooled...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28407661/effect-of-saxagliptin-on-circulating-endothelial-progenitor-cells-and-endothelial-function-in-newly-diagnosed-type-2-diabetic-patients
#9
Fang Li, Jiachao Chen, Fei Leng, Zhiqiang Lu, Yan Ling
Endothelial dysfunction is associated with the risk of cardiovascular complications in diabetic patients. Endothelial progenitor cells (EPCs) and flow-mediated dilation (FMD) are common markers of endothelial function. In this study, we aim to investigate whether the DPP-4 inhibitor saxagliptin modulate EPCs number and FMD in newly diagnosed, treatment-naive type 2 diabetic patients. This was a controlled, randomized, open-label clinical trial. Saxagliptin group and metformin group consumed either saxagliptin 5 mg per day or metformin 1 500 mg per day respectively for 12 weeks...
April 13, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28403877/a-comparison-of-effects-of-dpp-4-inhibitor-and-sglt2-inhibitor-on-lipid-profile-in-patients-with-type-2-diabetes
#10
Seon-Ah Cha, Yong-Moon Park, Jae-Seung Yun, Tae-Seok Lim, Ki-Ho Song, Ki-Dong Yoo, Yu-Bae Ahn, Seung-Hyun Ko
BACKGROUND: Previous studies suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different effects on the lipid profile in patients with type 2 diabetes. We investigated the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in patients with type 2 diabetes. METHODS: From January 2013 to December 2015, a total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were consecutively enrolled...
April 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#11
REVIEW
André J Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced...
March 25, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28402172/rational-design-and-synthesis-of-affinity-matrices-based-on-proteases-immobilized-onto-cellulose-membranes
#12
Alberto Del Monte-Martínez, Jorge González-Bacerio, Bessy Cutiño-Avila, Jorge Rojas, Mae Chappé, Emir Salas-Sarduy, Isel Pascual, José M Guisán
Discovery of new protease inhibitors may result in potential therapeutic agents or useful biotechnological tools. Obtainment of these molecules from natural sources requires simple, economic and highly efficient purification protocols. The aim of this work was the obtainment of affinity matrices by the covalent immobilization of dipeptidyl peptidase IV (DPP-IV) and papain onto cellulose membranes, previously activated with formyl (FCM) or glyoxyl groups (GCM). GCM showed the highest activation grade (10.2 µmol aldehyde/cm(2))...
April 12, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28387100/-about-the-choice-between-a-dpp-4-inhibitor-and-a-sglt-2-inhibitor-tor-treating-type-2-diabetes
#13
REVIEW
A J Scheen, N Paquot
Two new classes of oral antidiabetic agents play an increasing role in the management of type 2 diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and sodiumglucose cotransporters type 2 (SGLT2) inhibitors (gliflozins). After failure of a monotherapy with metformin (first pharmacological choice in type 2 diabetes), both may offer an alternative to the add-on of a sulphonylurea, especially in patients at risk of hypoglycaemia. However, the choice between a DPP-4 inhibitor and a SGLT2 inhibitor is not easy and should be oriented based upon the individual patient characteristics...
December 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28385659/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-sitagliptin-as-an-add-on-to-metformin-thiazolidinediones-or-both-in-patients-with-type-2-diabetes-sustain-2-a-56-week-double-blind-phase-3a-randomised-trial
#14
Bo Ahrén, Luis Masmiquel, Harish Kumar, Mehmet Sargin, Julie Derving Karsbøl, Sanja Hald Jacobsen, Francis Chow
BACKGROUND: Semaglutide is a novel glucagon-like peptide-1 (GLP-1) analogue, suitable for once-weekly subcutaneous administration, in development for treatment of type 2 diabetes. We assessed the efficacy and safety of semaglutide versus the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin, thiazolidinediones, or both. METHODS: We did a 56-week, phase 3a, randomised, double-blind, double-dummy, active-controlled, parallel-group, multinational, multicentre trial (SUSTAIN 2) at 128 sites in 18 countries...
May 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28378919/ethnic-difference-in-the-pharmacodynamics-efficacy-relationship-of-dipeptidyl-peptidase-4-inhibitors-between-japanese-and-non-japanese-patients-a-systematic-review
#15
Yuka Ito, Kaori Ambe, Mayu Kobayashi, Masahiro Tohkin
A systematic review of the differences in the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors between Japanese and non-Japanese subjects was conducted. We searched for randomized controlled trials in patients with type 2 diabetes mellitus which studied the intervention of a DPP-4 inhibitor once-daily versus placebo, as monotherapy or as add-on therapy. Data regarding placebo-corrected HbA1c reduction and trough DPP-4 inhibition rate after >=12 weeks' treatment were extracted. In the 12 eligible studies, linear regression analysis revealed that the HbA1c reduction at each DPP-4 inhibition level was larger in studies involving Japanese patients than in studies involving non-Japanese patients, with statistical significance between the two groups (p<0...
April 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28375658/empagliflozin-linagliptin-single-pill-combination-therapy-for-patients-with-type-2-diabetes-mellitus
#16
Rajeev Kumar Jain
Type 2 diabetes mellitus (T2DM) is typically progressive, with sequential addition of therapies often needed to address increasing hyperglycemia over the disease course. Using treatments in combination may be preferred to sequential addition, as a means of providing a more rapid clinical response and potentially avoiding clinical inertia. In such cases, a single-pill combination can help to reduce pill burden. Although various single-pill combinations of oral glucose-lowering agents are available, empagliflozin/linagliptin was the first approved combination of a sodium glucose co-transporter 2 (SGLT2) inhibitor with a dipeptidyl peptidase 4 (DPP-4) inhibitor in the United States...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28371205/efficacy-and-safety-of-tofogliflozin-in-japanese-patients-with-type-2-diabetes-mellitus-with-inadequate-glycaemic-control-on-insulin-therapy-j-step-ins-results-of-a-16-week-randomized-double-blind-placebo-controlled-multicentre-trial
#17
Yasuo Terauchi, Masahiro Tamura, Masayuki Senda, Ryoji Gunji, Kohei Kaku
AIMS: To assess the effects of 16 weeks of tofogliflozin (sodium/glucose co-transporter 2 (SGLT2) inhibitor) treatment versus placebo on glycosylated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase-4 (DPP-4) inhibitor. METHODS: This study comprises a 16-week, multicentre, double-blind, placebo-controlled period and a 36-week extension (NCT02201004)...
March 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28358275/demographic-and-clinical-profiles-of-type-2-diabetes-mellitus-patients-initiating-sitagliptin-in-the-real-world-setting
#18
Manjiri Pawaskar, Jinan Liu, Swapnil Rajpathak, Kristy Iglay, Samuel S Engel, Hakima Hannachi
OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been used for the management of type 2 diabetes (T2D) for over a decade; however, there is a limited understanding of the evolution of their use in the real world setting over this time period. This study evaluated the demographics, and clinical characteristics of patients initiating sitagliptin over a 10-year period in the United States. RESEARCH DESIGN AND METHODS: Quintiles electronic medical records database was used to identify adults with a new prescription of sitagliptin over two 5-year time periods: 2006-2010 (n = 57,604), and 2011-2015 (n = 147,326)...
March 30, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28356045/pathophysiological-implications-of-dipeptidyl-peptidases
#19
Akira Sato, Hisakazu Ogita
Dipeptidyl peptidases (DPPs) belong to one of the protease families classified under EC 3.4.14 in the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. DPPs family consists of eight members in the mammalian species. They play a role in oligopeptide N-terminal processing and degradation of bioactive peptides. Over the past 20 years, most of the studies have been focused on DPP 4 that has important roles in metabolism and immunity. A large number of pharmacological inhibitors against DPP 4 have been tested rigorously and some of them are now used in the treatment of type 2 diabetes and obesity...
March 29, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28355570/pancreatic-%C3%AE-cell-derived-glucagon-related-peptides-are-required-for-%C3%AE-cell-adaptation-and-glucose-homeostasis
#20
Shuyang Traub, Daniel T Meier, Friederike Schulze, Erez Dror, Thierry M Nordmann, Nicole Goetz, Norina Koch, Elise Dalmas, Marc Stawiski, Valmir Makshana, Fabrizio Thorel, Pedro L Herrera, Marianne Böni-Schnetzler, Marc Y Donath
Pancreatic α cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects of locally derived insulin secretagogues on β cell function and glucose homeostasis using mice with α cell ablation and with α cell-specific GLP-1 deficiency. Normally, intestinal GLP-1 compensates for the lack of α cell-derived GLP-1. However, upon aging and metabolic stress, glucose tolerance is impaired...
March 28, 2017: Cell Reports
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