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https://www.readbyqxmd.com/read/28522196/impact-of-glucose-lowering-therapies-on-risk-of-stroke-in-type-2-diabetes
#1
REVIEW
F Bonnet, A J Scheen
Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs...
May 15, 2017: Diabetes & Metabolism
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
#2
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/28472488/geographical-variation-in-anti-diabetic-prescribing-in-ireland-in-2013-and-2014-a-cross-sectional-analysis
#3
Mark E Murphy, Kathleen Bennett, Tom Fahey, Susan M Smith
Background.: Several new medications for type 2 diabetes (T2DM) have been introduced, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor (GLP-1) agonists. Variation in the prescribing of these agents has implications for quality, safety and costs. We aimed to investigate geographical variation in the prescribing of anti-diabetic medications in Ireland. Methods.: Cross-sectional analyses were undertaken on the two main national pharmacy claims databases in Ireland in 2013 and 2014...
May 2, 2017: Family Practice
https://www.readbyqxmd.com/read/28452143/zy15557-a-novel-long-acting-dpp-4-inhibitor-for-the-treatment-of-type-2-diabetes-mellitus
#4
M R Jain, A A Joharapurkar, S G Kshirsagar, V J Patel, R H Bahekar, H V Patel, P A Jadav, P R Patel, R C Desai
BACKGROUND AND PURPOSE: Dipeptidylpeptidase 4 (DPP-4) inhibitors increase levels of glucagon-like peptide -1 (GLP-1) and provide clinical benefit in the treatment of type 2 diabetes mellitus. Since longer acting inhibitors have therapeutic advantage, 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 using in vitro and in vivo preclinical models...
April 27, 2017: British Journal of Pharmacology
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
#5
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
#6
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
#7
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
#8
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
#9
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 February 1, 2014-June 30, 2014 were identified from the QuintilesIMS PharMetrics Plus Database...
May 8, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#10
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/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
#11
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/28355570/pancreatic-%C3%AE-cell-derived-glucagon-related-peptides-are-required-for-%C3%AE-cell-adaptation-and-glucose-homeostasis
#12
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
https://www.readbyqxmd.com/read/28347868/teneligliptin-a-dipeptidyl-peptidase-4-inhibitor-attenuated-pro-inflammatory-phenotype-of-perivascular-adipose-tissue-and-inhibited-atherogenesis-in-normoglycemic-apolipoprotein-e-deficient-mice
#13
Hotimah Masdan Salim, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Michio Shimabukuro, Masataka Sata
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis. METHODS AND RESULTS: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE(-/-)) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0...
March 24, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28344207/dipeptidyl-peptidase-iv-inhibition-for-the-treatment-of-cardiovascular-disease%C3%A3-recent-insights-focusing-on-angiogenesis-and-neovascularization
#14
Yanna Lei, Lina Hu, Guang Yang, Limei Piao, Minggen Jin, Xianwu Cheng
Dipeptidyl peptidase IV (DPP-IV) is a complex enzyme that acts as a membrane-anchored cell surface exopeptidase and transmits intracellular signals through a small intracellular tail. DPP-IV exists in human blood in a soluble form, and truncates a large number of peptide hormones, chemokines, cytokines, and growth factors in vitro and in vivo. DPP-IV has gained considerable interest as a therapeutic target, and a variety of DPP-IV inhibitors that prolong the insulinotropic effects of glucagon-like peptide-1 (GLP-1) are widely used in clinical settings as antidiabetic drugs...
March 25, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#15
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
April 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28276972/pharmacotherapy-of-treatment-resistant-type-2-diabetes
#16
REVIEW
André J Scheen
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28251513/intensifying-treatment-beyond-monotherapy-in-type-2-diabetes-mellitus-where-do-newer-therapies-fit
#17
REVIEW
Alexander Kuhn, Jean Park, Adline Ghazi, Vanita R Aroda
PURPOSE OF REVIEW: Guidelines for a standard second diabetes medication for the treatment of type 2 diabetes (T2DM) have yet to be established. The rapid increase in the number of newer therapies available makes the choice more difficult. Thus, we reviewed clinical trial evidence evaluating newer therapies available for treatment intensification beyond monotherapy. RECENT FINDINGS: Head-to-head studies comparing newer therapies versus traditional (i.e., sulfonylurea) approaches consistently find lower incidence of hypoglycemia and weight gain with newer therapies...
March 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28251104/effect-of-dipeptidyl-peptidase-4-inhibitors-on-acute-and-subacute-models-of-inflammation-in-male-wistar-rats-an-experimental-study
#18
Urmila Anil Kagal, Netravathi Basavaraj Angadi, Somnath Mallikarjun Matule
INTRODUCTION: The prevalence of Type 2 diabetes mellitus (T2DM) has reached alarming proportions due to the rapidly increasing rates of this disease worldwide. Preclinical and clinical studies have revealed elevated levels of inflammatory markers in a vast number of illnesses such as T2DM, obesity, and atherothrombosis collectively called metabolic syndrome leading to adverse cardiovascular events. Dipeptidyl peptidase 4 (DPP-4) inhibitors which are the enhancers of glucagon-like peptide 1 (GLP -1), could have anti-inflammatory potential which could help in reducing cardiovascular complications of diabetes and benefit patients suffering from the metabolic syndrome...
January 2017: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/28249585/incretin-based-agents-in-type-2-diabetic-patients-at-cardiovascular-risk-compare-the-effect-of-glp-1-agonists-and-dpp-4-inhibitors-on-cardiovascular-and-pancreatic-outcomes
#19
Zeqing Zhang, Xi Chen, Puhan Lu, Jianhua Zhang, Yongping Xu, Wentao He, Mengni Li, Shujun Zhang, Jing Jia, Shiying Shao, Junhui Xie, Yan Yang, Xuefeng Yu
BACKGROUND: Incretin-based agents, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 agonists (GLP-1As), work via GLP-1 receptor for hyperglycemic control directly or indirectly, but have different effect on cardiovascular (CV) outcomes. The present study is to evaluate and compare effects of incretin-based agents on CV and pancreatic outcomes in patients with type 2 diabetes mellitus (T2DM) and high CV risk. METHODS: Six prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia...
March 1, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28223856/uncertainties-around-incretin-based-therapies-a-literature-review
#20
REVIEW
Bader Al Tulaihi, Samia Alhabib
Background: Diabetes mellitus is a chronic debilitating and non-communicable disease. It has several long-term outcomes that are associated with various end organ damage, mainly the heart, blood vessels, eyes, nerves, and kidneys. There are different modalities of treatment of diabetes. The recent incretin-based therapies provided an innovative class of drugs including GLP-1 receptor agonists and DPP-4 inhibitors. This review aims to summarize the available evidence of their effectiveness. Method: This is a narrative review...
January 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
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