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https://www.readbyqxmd.com/read/28097882/antidiabetic-agents-and-cardiovascular-outcomes-in-patients-with-heart-diseases
#1
Judy W M Cheng, Hisham A Badreldin, Dhiren K Patel, Snehal H Bhatt
This article reviews evidence of benefits and risk of antidiabetic agents in cardiovascular (CV) outcomes, with a focus on medications approved by the FDA since 2008. Peer-reviewed articles were identified from MEDLINE and Current Content database (both 1966 to October 1, 2016) using the search terms insulin, metformin, rosiglitazone, pioglitazone, glyburide, glipizide, glimepiride, acarbose, miglitol, albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide, pramlintide, meglitinide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, colesevalam, bromocriptine, mortality, myocardial infarction (MI), heart failure, (HF) and stroke...
January 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28075066/efficacy-and-safety-of-fixed-dose-combination-therapy-alogliptin-plus-metformin-in-asian-patients-with-type-2-diabetes-a-phase-3-trial
#2
Linong Ji, Ling Li, Jian Kuang, Tao Yang, Dong-Jun Kim, Azidah Abdul Kadir, Chien-Ning Huang, Douglas Lee
This study evaluated the efficacy and safety of 26 weeks of twice-daily (BID) alogliptin + metformin fixed-dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 - 75 years with hemoglobin A1c (HbA1c) 7.5 - 10.0% after ≥2 months of diet and exercise and a 4-week placebo run-in were enrolled. Eligible patients were randomized (1:1:1:1) to placebo, alogliptin 12.5 mg BID, metformin 500 mg BID, or alogliptin 12.5 mg plus metformin 500 mg FDC BID. The primary endpoint was change in HbA1c from baseline to end of treatment (Week 26)...
January 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28058763/relationship-of-glycated-haemoglobin-and-reported-hypoglycaemia-to-cardiovascular-outcomes-in-patients-with-type-2-diabetes-and-recent-acute-coronary-syndromes-the-examine-trial
#3
Simon R Heller, Richard M Bergenstal, William B White, Stuart Kupfer, George L Bakris, William C Cushman, Cyrus R Mehta, Steven E Nissen, Craig A Wilson, Faiez Zannad, Yuyin Liu, Noah M Gourlie, Christopher P Cannon
AIMS: To investigate relationships between glycated haemoglobin (HbA1c) and reported hypoglycaemia and risk of major adverse cardiovascular (CV) events (MACE). METHODS: The EXAMINE trial randomized 5380 patients in 49 countries with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) to double-blind treatment with alogliptin or placebo in addition to standard of care. We used Cox proportional hazards models to analyze relationships among MACE, HbA1c levels and hypoglycaemia events...
January 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27999883/the-pharmacokinetics-and-pharmacodynamics-of-alogliptin-in-children-adolescents-and-adults-with-type-2-diabetes-mellitus
#4
Caroline Dudkowski, Max Tsai, Jie Liu, Zhen Zhao, Eric Schmidt, Jeannie Xie
PURPOSE: The aim of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 12.5- or 25-mg dose of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in pediatric (children and adolescents) and adult subjects with type 2 diabetes mellitus (T2DM). METHODS: A randomized, open-label, multicenter study was conducted in pediatric and adult subjects. Subjects in two pediatric groups (children and adolescents) were randomized 1:1 to receive a single oral dose of alogliptin 12...
December 20, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27979881/an-update-on-the-gliptins
#5
(no author information available yet)
Progressive impairment of insulin secretion in people with type 2 diabetes leads to blood glucose concentrations worsening over time, often resulting in escalation of blood glucose lowering therapy.(1) In 2015/2016, more money was spent on dipeptidyl peptidase-4 (DPP-4) inhibitors ('gliptins') than on any other class of antidiabetic drug except for insulins.(2) In 2008, we reviewed sitagliptin and vildagliptin.(3) Here, we briefly review three other DPP-4 inhibitors, saxagliptin (Onglyza-AstraZeneca), linagliptin (Trajenta-Boehringer Ingelheim) and ▼alogliptin (Vipidia-Takeda), and consider data from recent cardiovascular outcomes studies...
December 2016: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/27976813/evaluation-of-drug-efficacy-of-dpp-4-inhibitors-based-on-theoretical-analysis-with-pharmacokinetics-and-pharmacodynamics
#6
Risa Takayanagi, Takumi Uchida, Koji Kimura, Yasuhiko Yamada
Dipeptidyl peptidase-4 (DPP-4) inhibitors are used clinically as therapeutic agents for treatment of diabetes. To determine the rate of DPP-4 inhibition induced by these inhibitors, we used pharmacokinetic and pharmacodynamic parameters to theoretically examine the relationship between the rate of DPP-4 inhibition and clinical efficacy following administration of 4 different DPP-4 inhibitors (sitagliptin, vildagliptin, alogliptin, linagliptin) by focusing on the increase in level of glucagon-like peptide-1 (GLP-1) induced by their administration...
December 15, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27930863/lessons-from-a-cardiovascular-outcome-trial-with-liraglutide-in-type-2-diabetes
#7
Hae Jin Kim, Dae Jung Kim
Cardiovascular disease (CVD) is the leading cause of death and one of common diabetes-related complications in patients with type 2 diabetes(1) . After the US Food and Drug Administration issued guidelines for assessing the CVD risk of all new glucose-lowering agents for type 2 diabetes in 2008(2) , randomized controlled CV outcome trials with new antidiabetic drugs, such as the dipeptidyl peptidase-4 inhibitors (saxagliptin, alogliptin, and sitagliptin) and the glucagon-like peptide-1 receptor agonist (GLP-1 RA), lixisenatide, showed CV safety in high CV risk patient populations with type 2 diabtes(3) ...
December 8, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27918671/dpp-4-inhibitor-treatment-in-chinese-type-2-diabetes-patients-a-meta-analysis
#8
Xiaoling Cai, Xueying Gao, Wenjia Yang, Yifei Chen, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
BACKGROUND: The aim of this meta-analysis was to assess the comprehensive clinical efficacy of dipeptidyl peptidase-IV (DPP-4) inhibitors in Chinese type 2 diabetes patients and to evaluate whether there is a different response to treatment with different kinds of DPP-4 inhibitors in those patients. METHODS: Databases were systematically searched, and qualifying clinical studies of Chinese type 2 diabetes patients were included. RESULTS: A total of 30 studies were included...
December 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27891757/randomized-double-blind-phase-iii-study-to-evaluate-the-efficacy-and-safety-of-once-daily-treatment-with-alogliptin-and-metformin-hydrochloride-in-japanese-patients-with-type-2-diabetes
#9
Kohei Kaku, Shuuji Sumino, Masafumi Katou, Yuya Nishiyama, Yoshinobu Kinugawa
This randomized, double-blind, phase III study evaluated the efficacy and safety of once-daily treatment with alogliptin (25 mg once daily), alone or with metformin hydrochloride (500 mg once daily or 250 mg twice daily), in Japanese patients with type 2 diabetes. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to the end of treatment (week 24). The least squares (LS) mean (standard error) change in HbA1c from baseline to the end of treatment (week 24) was 0.16 (0.072)% in alogliptin alone, -0...
November 28, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27844335/cardiovascular-safety-of-incretin-based-therapies-in-type-2-diabetes-systematic-review-of-integrated-analyses-and-randomized-controlled-trials
#10
REVIEW
Edoardo Mannucci, Matteo Monami
INTRODUCTION: Regulatory requirements mandate that new drugs for treatment of patients with type 2 diabetes mellitus (T2DM), such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, are evaluated to show that they do not increase cardiovascular (CV) risk. METHODS: A systematic review was undertaken to evaluate the association between DPP-4 inhibitor and GLP-1 receptor agonist use and major adverse cardiac events (MACE)...
January 2017: Advances in Therapy
https://www.readbyqxmd.com/read/27835045/cardiovascular-outcomes-of-new-medications-for-type-2-diabetes
#11
Jennifer M Trujillo, Sara A Wettergreen, Wesley A Nuffer, Samuel L Ellis, Michael T McDermott
Cardiovascular (CV) disease remains the leading cause of death in people with diabetes, highlighting the importance of using treatment options that do not increase CV risk or possibly decrease CV outcomes. Since 2008, the Food and Drug Administration has required demonstration of CV safety for all new medications developed for the glycemic management of diabetes. Seven trials have been published that have established CV safety for three DPP-4 inhibitors (alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists (liraglutide, lixisenatide, and semaglutide), and one sodium-glucose cotransporter-2 inhibitor (empagliflozin)...
December 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27832184/comparative-binding-analysis-of-dipeptidyl-peptidase-iv-dpp-4-with-antidiabetic-drugs-an-ab-initio-fragment-molecular-orbital-study
#12
Sundaram Arulmozhiraja, Naoya Matsuo, Erika Ishitsubo, Seiji Okazaki, Hitoshi Shimano, Hiroaki Tokiwa
Dipeptidyl peptidase IV (DPP-4) enzyme is responsible for the degradation of incretins that stimulates insulin secretion and hence inhibition of DPP-4 becomes an established approach for the treatment of type 2 diabetics. We studied the interaction between DPP-4 and its inhibitor drugs (sitagliptin 1, linagliptin 2, alogliptin 3, and teneligliptin 4) quantitatively by using fragment molecular orbital calculations at the RI-MP2/cc-pVDZ level to analyze the inhibitory activities of the drugs. Apart from having common interactions with key residues, inhibitors encompassing the DPP-4 active site extensively interact widely with the hydrophobic pocket by their hydrophobic inhibitor moieties...
2016: PloS One
https://www.readbyqxmd.com/read/27796904/strategies-for-diabetes-management-using-newer-oral-combination-therapies-early-in-the-disease
#13
REVIEW
Joel Zonszein, Per-Henrik Groop
INTRODUCTION: The duration of uncontrolled type 2 diabetes mellitus (T2DM) can adversely impact small and large vessels, eventually leading to microvascular and macrovascular complications. Failure of therapeutic lifestyle changes, monotherapy, and clinical inertia contribute to persistent hyperglycemia and disease progression. The aim was to review the complex pathophysiology of type 2 diabetes and how different oral agents can be used effectively as first-line therapy in combination with metformin, as well as in patients not achieving glycemic goals with metformin therapy...
December 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27787778/the-cost-effectiveness-of-alogliptin-versus-sulfonylurea-as-add-on-therapy-to-metformin-in-patients-with-uncontrolled-type-2-diabetes-mellitus
#14
Jason Gordon, Phil McEwan, Michael Hurst, Jorge Puelles
INTRODUCTION: ENDURE (ClinicalTrials.gov identifier, NCT00856284), a multicenter, double-blind, active-controlled study of 2639 patients with uncontrolled type 2 diabetes mellitus (T2DM), found that metformin in combination with alogliptin (12.5 and 25 mg doses), when compared to standard add-on therapy (sulfonylurea, SU), exerted sustained antihyperglycemic effects over 2 years. This economic analysis of ENDURE aimed to quantify the relationship between increased glycemic durability and cost-effectiveness of alogliptin in the UK clinical setting, and communicate its sustained glycemic benefit in economic terms...
December 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27714283/synthesis-and-biological-evaluation-of-triazole-based-uracil-derivatives-as-novel-dpp-4-inhibitors
#15
Qing Li, Li Han, Bin Zhang, Jinpei Zhou, Huibin Zhang
A series of triazole based uracil derivatives were designed and synthesized as novel DPP-4 inhibitors. Compound A01 was identified as a lead compound for SAR studies focused on the structural modification at the S2' subsite of DPP-4. The novel analogues A02-A25 were obtained by modifying the substituents at the phenyl group, and B01-B09, by introducing the carbonyl group. On screening in DPP-4, compounds B03, B04 and B08 showed a significant improvement in DPP-4 inhibitory activities compared to compound A01 and showed comparable activities to the marketed DPP-4 inhibitor, alogliptin...
October 12, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27665059/drug-drug-interactions-between-immunosuppressants-and-antidiabetic-drugs-in-the-treatment-of-post-transplant-diabetes-mellitus
#16
REVIEW
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/27659407/combined-analysis-of-three-large-interventional-trials-with-gliptins-indicates-increased-incidence-of-acute-pancreatitis-in-patients-with-type-2-diabetes
#17
Ivan Tkáč, Itamar Raz
OBJECTIVE: Data on the possible relationship of gliptin treatment to the incidence of acute pancreatitis have been controversial. The aim of the current study was to combine data on the incidence of acute pancreatitis from three large randomized controlled trials. RESEARCH DESIGN AND METHODS: Three trials designed to test cardiovascular safety and efficacy of add-on treatment with a gliptin were included in the analysis, as follows: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin)...
September 22, 2016: Diabetes Care
https://www.readbyqxmd.com/read/27612317/cardiovascular-safety-trials-of-incretin-based-drugs-what-do-they-mean
#18
Daisuke Yabe, Yutaka Seino
Incretin-based dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are newer choices of antidiabetic medications that are now most widely used worldwide. Preclinical study results suggest that the two drugs potentially exert benefits to prevent onsets and/or progressions of diabetes-related complications, such as myocardial infarctions and strokes. Outcomes of five clinical trials to evaluate the cardiovascular (CV) safety of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonist have been recently reported...
September 9, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27608919/degradation-kinetics-study-of-alogliptin-benzoate-in-alkaline-medium-by-validated-stability-indicating-hptlc-method
#19
Shailesh Shah, Bhavin Marolia, Pintu Prajapati, Kunjan Bharatkumar Bodiwala, Jeenal Thakor
A rapid, sensitive, and stability-indicating high-performance thin-layer chromatographic method was developed and validated to study degradation kinetics of Alogliptin benzoate (ALG) in an alkaline medium. ALG was degraded under acidic, alkaline, oxidative, and thermal stress conditions. The degraded samples were chromatographed on silica gel 60F254-TLC plates, developed using a quaternary-solvent system (chloroform-methanol-ethyl acetate-triethyl amine, 9+1+1+0.5, v/v/v/v), and scanned at 278 nm. The developed method was validated per International Conference on Harmonization guidelines using validation parameters such as specificity, linearity and range, precision, accuracy, LOD, and LOQ...
September 7, 2016: Journal of AOAC International
https://www.readbyqxmd.com/read/27573605/inhibition-of-dpp-4-by-alogliptin-improves-coronary-flow-reserve-and-left-ventricular-systolic-function-evaluated-by-phase-contrast-cine-magnetic-resonance-imaging-in-patients-with-type-2-diabetes-and-coronary-artery-disease
#20
Shingo Kato, Kazuki Fukui, Hidekuni Kirigaya, Daiki Gyotoku, Naoki Iinuma, Yuka Kusakawa, Kohei Iguchi, Tatsuya Nakachi, Tae Iwasawa, Kazuo Kimura
BACKGROUND: The present study determined whether dipeptidyl peptidase-4 (DPP-4) inhibition by alogliptin improves coronary flow reserve (CFR) and left ventricular election fraction (LVEF) in patients with type 2 DM and CAD. MATERIALS AND METHODS: Twenty patients with type 2 DM and known or suspected CAD were randomly allocated to receive diet therapy plus alogliptin (n=10; mean age, 73.3±6.6y) or a control group given diet therapy and glimepiride (n=10; mean age, 76...
November 15, 2016: International Journal of Cardiology
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