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https://www.readbyqxmd.com/read/27918671/dpp-4-inhibitor-treatment-in-chinese-type-2-diabetes-patients-a-meta-analysis
#1
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 5, 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27891757/a-randomized-double-blind-phase-iii-study-to-evaluate-efficacy-and-safety-of-once-daily-treatment-of-alogliptin-and-metformin-hydrochloride-in-japanese-patients-with-type-2-diabetes
#2
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 (q.d.) treatment of alogliptin (25 mg q.d.) alone or with metformin hydrochloride (500 mg q.d. or 250 mg twice daily [b.i.d.]) in Japanese patients with type 2 diabetes. The primary endpoint was change in haemoglobin A1c (HbA1c) from baseline to the end of treatment (week 24). The least-squares mean (LSM) change in HbA1c from baseline (standard error) 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
#3
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)...
November 14, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27835045/cardiovascular-outcomes-of-new-medications-for-type-2-diabetes
#4
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)...
November 11, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27537577/the-effect-of-alogliptin-on-pulmonary-function-in-obese-patients-with-type-2-diabetes-inadequately-controlled-by-metformin-monotherapy
#14
He Tai, Ming-Yue Wang, Yue-Ping Zhao, Ling-Bing Li, Qian-Yan Dong, Xin-Guang Liu, Jin-Song Kuang
BACKGROUND: To observe the effect of alogliptin combined with metformin on pulmonary function in obese patients with type 2 diabetes inadequately controlled by metformin monotherapy (500 mg, bid po, for at least 3 months), and evaluate its efficacy and safety. METHODS: After a 2-week screening period, adult patients (aged 36-72 years) entered a 4-week run-in/stabilization period. Then, patients were randomly assigned to either the intervention group (n = 55) or the control group (n = 50) for 26 weeks...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27509090/dipeptidyl-peptidase-iv-inhibitor-alogliptin-improves-stress-induced-insulin-resistance-and-prothrombotic-state-in-a-murine-model
#15
Maimaiti Yisireyili, Kyosuke Takeshita, Motoharu Hayashi, Hongxian Wu, Yasuhiro Uchida, Koji Yamamoto, Ryosuke Kikuchi, Chang-Ning Hao, Takayuki Nakayama, Xian Wu Cheng, Tadashi Matsushita, Shigeo Nakamura, Toyoaki Murohara
BACKGROUND: Stress evokes lipolytic release of free fatty acid (FFA) and low-grade inflammation in visceral adipose tissue, mediated by increased adipokine secretion, and contributes to glucose metabolism disorder and prothrombotic state. We tested the hypothesis that alogliptin, a dipeptidyl peptidase-4 inhibitor, can ameliorate the biological effects of chronic stress in mice. METHOD AND RESULTS: C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle or alogliptin (dose: 15 or 45mg/kg/day)...
November 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27491279/demographic-and-clinical-characteristics-of-patients-with-type-2-diabetes-mellitus-initiating-dipeptidyl-peptidase-4-inhibitors-a-retrospective-study-of-uk-general-practice
#16
Abigail Tebboth, Sally Lee, Anna Scowcroft, Paula Bingham-Gardiner, Will Spencer, John Bolodeoku, Syed Wasi Hassan
PURPOSE: The majority of people with type 2 diabetes mellitus (T2DM) will develop chronic kidney disease in their lifetime. Because most dipeptidyl peptidase (DPP)-4 inhibitors require dose adjustment in patients with T2DM and renal impairment, we aimed to understand how these treatments are prescribed in UK clinical practice, and to determine whether recommended dose adjustments are being made at initial prescription. METHODS: This retrospective, descriptive cohort study analyzed data from the Clinical Practice Research Datalink (CPRD)...
August 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27373139/novel-antidiabetic-drugs-and-cardiovascular-risk-primum-non-nocere
#17
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27372109/omarigliptin-for-the-treatment-of-type-2-diabetes
#18
Xueying Tan
Omarigliptin is a new once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of type 2 diabetes. It is indicated to have favorable effects on glycosylated hemoglobin (HbA1c), fasting and postmeal plasma glucose. It potently but reversibly inhibits DPP-4 enzyme, which prolongs the circulating half-life of glucagon-like peptide-1 that increases insulin secretion in a glucose-dependent manner. Benefiting from glucose-dependent insulin secretion, omarigliptin is associated with low risk of hypoglycemia...
July 2, 2016: Endocrine
https://www.readbyqxmd.com/read/27347354/cardiovascular-safety-of-dipeptidyl-peptidase-4-inhibitors-recent-evidence-on-heart-failure
#19
Saumya Reddy Kankanala, Rafay Syed, Quan Gong, Boxu Ren, Xiaoquan Rao, Jixin Zhong
The cardiovascular safety of DPP4 inhibitors as a class, especially in regards to heart failure, has been questioned after the publication of first trials (SAVOR-TIMI 53 and EXAMINE) assessing the cardiovascular risks of DPP4 inhibitors alogliptin and sitagliptin in 2013. Although there were no increased risks in composite cardiovascular outcomes, the SAVOR-TIMI 53 trial reported a 27% increase in hospitalization for heart failure in diabetic patients who received the DPP4 inhibitor saxagliptin. There has been substantial increase in knowledge on the heart failure effect of DPP4 inhibition since 2013...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27328054/trelagliptin-syr-472-zafatek-novel-once-weekly-treatment-for-type-2-diabetes-inhibits-dipeptidyl-peptidase-4-dpp-4-via-a-non-covalent-mechanism
#20
Charles E Grimshaw, Andy Jennings, Ruhi Kamran, Hikaru Ueno, Nobuhiro Nishigaki, Takuo Kosaka, Akiyoshi Tani, Hiroki Sano, Yoshinobu Kinugawa, Emiko Koumura, Lihong Shi, Koji Takeuchi
Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor, shows sustained efficacy by once-weekly dosing in type 2 diabetes patients. In this study, we characterized in vitro properties of trelagliptin, which exhibited approximately 4- and 12-fold more potent inhibition against human dipeptidyl peptidase-4 than alogliptin and sitagliptin, respectively, and >10,000-fold selectivity over related proteases including dipeptidyl peptidase-8 and dipeptidyl peptidase-9. Kinetic analysis revealed reversible, competitive and slow-binding inhibition of dipeptidyl peptidase-4 by trelagliptin (t1/2 for dissociation ≈ 30 minutes)...
2016: PloS One
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