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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/27913576/empagliflozin-as-add-on-therapy-in-patients-with-type-2-diabetes-inadequately-controlled-with-linagliptin-and-metformin-a-24-week-randomized-double-blind-parallel-group-trial
#2
Eirik Søfteland, Juris J Meier, Bente Vangen, Robert Toorawa, Mario Maldonado-Lutomirsky, Uli C Broedl
OBJECTIVE: To evaluate the efficacy and safety of empagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with linagliptin and metformin. RESEARCH DESIGN AND METHODS: Patients with HbA1c ≥8.0% and ≤10.5% (≥64 and ≤91 mmol/mol) while receiving stable-dose metformin received open-label linagliptin 5 mg (n = 606) for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (≥53 and ≤91 mmol/mol) were randomized to receive double-blind, double-dummy treatment with empagliflozin 10 mg (n = 112), empagliflozin 25 mg (n = 111), or placebo (n = 110) for 24 weeks; all patients continued treatment with metformin and linagliptin 5 mg...
December 2, 2016: Diabetes Care
https://www.readbyqxmd.com/read/27895822/linagliptin-alleviates-fatty-liver-disease-in-diabetic-db-db-mice
#3
Svetlana V Michurina, Irina Ju Ishenko, Vadim V Klimontov, Sergey A Archipov, Natalia E Myakina, Marina A Cherepanova, Eugenii L Zavjalov, Galina V Koncevaya, Vladimir I Konenkov
AIM: To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease (NAFLD) in db/db mice. METHODS: Male diabetic db/db mice (BKS.Cg-Dock7(m+)/(+)Lepr(db)/J) aged 10 wk received the dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin (10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals...
November 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/27875385/effects-of-linagliptin-on-vessel-wall-healing-in-the-rat-model-of-arterial-injury-under-normal-and-diabetic-conditions
#4
Linnea Eriksson, Samuel Röhl, Robert Saxelin, Mariette Lengquist, Malin Kronqvist, Kenneth Caidahl, Claes-Göran Östenson, Anton Razuvaev
Diabetic patients suffer an increased risk of restenosis and late stent thrombosis after angioplasty, complications that are related to a defective re-endothelialization. Dipeptidyl peptidase-4 inhibitors have been suggested to exert direct effect on endothelial and smooth muscle cells (SMCs). Therefore the objective was to study if the dipeptidyl peptidase-4 inhibitor linagliptin could influence vascular repair and accelerate re-endothelialization after arterial injury in healthy and diabetic animals. Diabetic Goto-Kakizaki and healthy Wistar rats were subjected to arterial injury and treated with linagliptin or vehicle...
November 17, 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/27868359/linagliptin-improves-endothelial-function-in-patients-with-type-2-diabetes-a-randomized-study-of-linagliptin-effectiveness-on-endothelial-function
#5
Fumika Shigiyama, Naoki Kumashiro, Masahiko Miyagi, Ryo Iga, Yuka Kobayashi, Eiichiro Kanda, Hiroshi Uchino, Takahisa Hirose
AIMS/INTRODUCTION: The present multicenter, prospective, controlled, open and randomized three-arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function. MATERIALS AND METHODS: Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add-on group, n = 29) and treated for 16 weeks...
October 19, 2016: Journal of Diabetes Investigation
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
#6
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/27823952/novel-findings-of-secreted-cyclophilin-a-in-diabetic-nephropathy-and-its-association-with-renal-protection-of-dipeptidyl-peptidase-4-inhibitor
#7
Shang-Feng Tsai, Chang-Chi Hsieh, Ming-Ju Wu, Cheng-Hsu Chen, Ting-Hui Lin, Mingli Hsieh
BACKGROUND: Our previous clinical indicated that urinary cyclophilin A was a good marker for diabetic nephropathy. METHODS: We used animal and cell models of diabetic nephropathy to examine the role of cyclophilin A in disease progression. RESULTS: Significantly increased urinary cyclophilin A could be detected in db/db at the 8th week. Linagliptin (3mg/kg/day and 15mg/kg/day) could suppress urinary 8-hydroxy-2'-deoxyguanosine at the 8th and 16th week but only the high dose Linagliption could suppress cyclophilin A at the 8th week...
December 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27800649/effects-of-dpp-4-inhibitor-linagliptin-and-glp-1-receptor-agonist-liraglutide-on-physiological-response-to-hypoglycemia-in-japanese-subjects-with-type-2-diabetes-a-randomized-open-label-2-arm-parallel-comparative-exploratory-trial
#8
Daisuke Yabe, Takashi Eto, Masanari Shiramoto, Shin Irie, Kenta Murotani, Yusuke Seino, Hitoshi Kuwata, Takeshi Kurose, Susumu Seino, Bo Ahren, Yutaka Seino
Dipeptidyl peptidase-4 (DPP-4) inhibitors reduces the risk of hypoglycemia, possibly through augmentation of glucose-dependent insulinotropic polypeptide (GIP) action but not that of glucagon-like peptide-1 (GLP-1) on glucagon secretion. To examine this model in Japanese individuals with type 2 diabetes (T2D), the effects of the DPP-4 inhibitor linagliptin on glucagon and other counterregulatory hormone responses to hypoglycemia were evaluated and compared with those of the GLP-1 receptor agonist liraglutide in a multi-center, randomized, open-label, 2 arm parallel comparative, exploratory trial...
November 1, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27796904/strategies-for-diabetes-management-using-newer-oral-combination-therapies-early-in-the-disease
#9
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/27763526/analytical-enantio-separation-of-linagliptin-in-linagliptin-and-metformin-hcl-dosage-forms-by-applying-two-level-factorial-design
#10
Sushant B Jadhav, Rahul M Mane, Kalyanraman L Narayanan, Popatrao N Bhosale
A novel, stability indicating, reverse phase high-performance liquid chromatography (RP-HPLC) method was developed to determine the S-isomer of linagliptin (LGP) in linagliptin and metformin hydrochloride (MET HCl) tablets (LGP-MET HCl) by implementing design of experiment (DoE), i.e., two-level, full factorial design (2³ + 3 centre points = 11 experiments) to understand the critical method parameters (CMP) and its relation with the critical method attribute (CMA), and to ensure robustness of the method. The separation of the S-isomer, LGP and MET HCl in the presence of their impurities was achieved on Chiralpak(®) IA-3 (Amylose tris (3, 5-dimethylphenylcarbamate), immobilized on 3 µm silica gel) stationary phase (250 × 4...
October 17, 2016: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/27762093/linagliptin-as-add-on-to-empagliflozin-and-metformin-in-patients-with-type-2-diabetes-two-24-week-randomized-double-blind-double-dummy-parallel-group-trials
#11
Francisco J Tinahones, Baptist Gallwitz, Matias Nordaby, Sophia Götz, Mario Maldonado-Lutomirsky, Hans J Woerle, Uli C Broedl
AIM: To evaluate the efficacy and safety of linagliptin versus placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with inadequate glycaemic control despite stable-dose metformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (>53 and ≤91 mmol/mol) (N = 482) were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg (study 1) or metformin and empagliflozin 25 mg (study 2)...
October 20, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27739231/phase-i-and-pharmacokinetic-drug-drug-interaction-study-of-metformin-losartan-and-linagliptin-coadministered-with-dw1029m-in-healthy-volunteers
#12
Seol Ju Moon, Sun-Young Kim, Cheol-Hee Lim, Hwan Bong Jang, Min-Gul Kim, Ji-Young Jeon
We investigated botanical drug-pharmaceutical drug interactions between DW1029 (a botanical extract of Morus alba linne root bark and Puerariae radix) and metformin, losartan, and linagliptin in the steady state. Three studies were conducted as a randomized, open-label, two-period, two-treatment, multiple-dose, two-way crossover designs. Eligible subjects received metformin (500 mg twice daily), losartan (50 mg once daily), or linagliptin (5 mg once daily) with DW1029M (300 mg × 2T twice daily) every 12 h on days 1 through 6 and a single dose in the morning of day 7...
October 14, 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27733180/the-effects-of-linagliptin-on-endothelial-function-and-global-arginine-bioavailability-ratio-in-coronary-artery-disease-patients-with-early-diabetes-study-protocol-for-a-randomized-controlled-trial
#13
Norbert J Tripolt, Felix Aberer, Regina Riedl, Barbara Hutz, Jasmin Url, Gudrun Dimsity, Andreas Meinitzer, Tatjana Stojakovic, Ronald Hödl, Marianne Brodmann, Franz Hafner, Harald Sourij
BACKGROUND: Patients with type 2 diabetes (T2DM) are at increased risk for macrovascular events as well as for microvascular complications. There is evidence that in patients with coronary artery disease (CAD), about 35 % suffer from manifest T2DM. Early glucose-lowering intervention in subjects with T2DM has been demonstrated to be beneficial in terms of cardiovascular risk reduction. But thus far, no data are available regarding investigating the impact of linagliptin treatment in patients with early diabetes on cardiovascular endpoints or surrogate parameters...
October 13, 2016: Trials
https://www.readbyqxmd.com/read/27710821/effects-of-linagliptin-monotherapy-compared-with-voglibose-on-postprandial-blood-glucose-responses-in-japanese-patients-with-type-2-diabetes-linagliptin-study-of-effects-on-postprandial-blood-glucose-l-step
#14
Yoshio Fujitani, Shimpei Fujimoto, Kiyohito Takahashi, Hiroaki Satoh, Takahisa Hirose, Toru Hiyoshi, Masumi Ai, Yosuke Okada, Masahiko Gosho, Tomoya Mita, Hirotaka Watada
AIMS: To compare the efficacy on glycemic parameters between a 12-week administration of once-daily linagliptin and thrice-daily voglibose in Japanese patients with type 2 diabetes. METHODS: In a multi-center, randomized, parallel-group study, 382 patients with diabetes were randomized to the linagliptin group (n=192) or the voglibose group (n=190). A meal tolerance test was performed at weeks 0 and 12. Primary outcomes were the change from baseline to week 12 in serum glucose levels at 2h during the meal tolerance test, HbA1c levels, and serum fasting glucose levels, which were compared between the 2 groups...
September 22, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27699599/linagliptin-a-dipeptidyl-peptidase-4-inhibitor-mitigates-cognitive-deficits-and-pathology-in-the-3xtg-ad-mouse-model-of-alzheimer-s-disease
#15
Jayasankar Kosaraju, R M Damian Holsinger, Lixia Guo, Kin Yip Tam
Glucagon-like peptide-1 (GLP-1) is an incretin hormone shown to be active in the treatment of type-2 diabetes (T2D) and has also been shown as efficacious in Alzheimer's disease (AD). Dipeptidyl peptidase-4 (DPP-4), an enzyme that is expressed in numerous cells, rapidly inactivates endogenous GLP-1. Therefore, DPP-4 inhibition is employed as a therapeutic avenue to increase GLP-1 levels in the management of T2D. The effectiveness of DPP-4 inhibitors in the treatment of AD has been reported in various animal models of AD...
October 3, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27684308/linagliptin-plus-metformin-in-patients-with-newly-diagnosed-type-2-diabetes-and-marked-hyperglycemia
#16
Stuart A Ross, A Enrique Caballero, Stefano Del Prato, Baptist Gallwitz, Diane Lewis-D'Agostino, Zelie Bailes, Sandra Thiemann, Sanjay Patel, Hans-Juergen Woerle, Maximilian von Eynatten
OBJECTIVES: Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population. METHODS: We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8...
September 29, 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27670099/scaffold-hopping-from-xanthines-to-tricyclic-guanines-a-case-study-of-dipeptidyl-peptidase-4-dpp4-inhibitors
#17
Dmitri A Pissarnitski, Zhiqiang Zhao, David Cole, Wen-Lian Wu, Martin Domalski, John W Clader, Giovanna Scapin, Johannes Voigt, Aileen Soriano, Theresa Kelly, Mary Ann Powles, Zuliang Yao, Duane A Burnett
Molecular modeling of unbound tricyclic guanine scaffolds indicated that they can serve as effective bioisosteric replacements of xanthines. This notion was further confirmed by a combination of X-ray crystallography and SAR studies, indicating that tricyclic guanine DPP4 inhibitors mimic the binding mode of xanthine inhibitors, exemplified by linagliptin. Realization of the bioisosteric relationship between these scaffolds potentially will lead to a wider application of cyclic guanines as xanthine replacements in drug discovery programs for a variety of biological targets...
November 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27660406/effects-and-safety-of-linagliptin-as-an-add-on-therapy-in-advanced-stage-diabetic-nephropathy-patients-taking-renin-angiotensin-aldosterone-system-blockers
#18
Yuichiro Ueda, Hiroki Ishii, Taisuke Kitano, Mitsutoshi Shindo, Haruhisa Miyazawa, Kiyonori Ito, Keiji Hirai, Yoshio Kaku, Honami Mori, Taro Hoshino, Susumu Ookawara, Masafumi Kakei, Kaoru Tabei, Yoshiyuki Morishita
BACKGROUND: We investigated the effects and safety of linagliptin as an add-on therapy in patients with advanced-stage diabetic nephropathy (DMN) taking renin-angiotensin-aldosterone system (RAAS) blockers. METHOD: Twenty advanced-stage DMN patients (estimated glomerular filtration rate (eGFR): 24.5 ± 13.4 mL/min/1.73 m(2)) taking RAAS blockers were administered 5 mg/day linagliptin for 52 weeks. Changes in glucose and lipid metabolism and renal function were evaluated...
2016: Drug Target Insights
https://www.readbyqxmd.com/read/27591880/effect-of-linagliptin-on-structural-changes-in-the-kidney-in-experimental-type-2-diabetes-mellitus
#19
Yu S Gavrilova, N P Bgatova, V V Klimontov, I Yu Ischenko, S V Michurina, N E Myakina, E L Zavyalov
Effect of the dipeptidyl peptidase-4 inhibitor linagliptin on structural manifestations of diabetic nephropathy was studied in BKS.Cg-Dock7m+/+Leprdb/J mice (experimental model of type 2 diabetes mellitus). Linagliptin (10 mg/kg per day) or vehicle was administered by gavage over 8 weeks. Mesangial expansion, thickening of the basement membrane in glomerular capillaries and proximal tubules, and retraction of cytopodia were less pronounced in mice receiving linagliptin. The protective effect of linagliptin on the kidney structure was not associated with its hypoglycemic action...
August 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27586249/effects-of-linagliptin-on-renal-endothelial-function-in-patients-with-type-2-diabetes-a-randomised-clinical-trial
#20
Christian Ott, Iris Kistner, Mirjam Keller, Stefanie Friedrich, Carsten Willam, Peter Bramlage, Roland E Schmieder
AIMS/HYPOTHESIS: Endothelial dysfunction predicts cardiovascular damage and renal involvement. Animal experiments and human studies indicate an increased nitric oxide (NO) activity and endothelial NO synthase (NOS) expression in the early stage of type 2 diabetes. The aim of the study was to assess the effect of linagliptin on the endothelial function of the renal vasculature. METHODS: In this randomised, double-blind, parallel-group, investigator-initiated trial, 62 patients with type 2 diabetes were randomly assigned (by computer-generated random code) to receive linagliptin 5 mg (n = 30) or placebo (n = 32) for 4 weeks...
December 2016: Diabetologia
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