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https://www.readbyqxmd.com/read/28088030/efficacy-and-safety-of-linagliptin-metformin-single-pill-combination-as-initial-therapy-in-drug-na%C3%A3-ve-asian-patients-with-type-2-diabetes
#1
Yiming Mu, Changyu Pan, Bei Fan, Uwe Hehnke, Xiuzhen Zhang, Xuejun Zhang, Xiaoyue Wang, Jingdong Liu, Ying Zhang, Jianling Du, Jianhua Ma, Yan Gong
AIM: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control. METHODS: Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2...
December 5, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28039605/pharmacokinetic-characteristics-and-clinical-efficacy-of-an-sglt2-inhibitor-plus-dpp-4-inhibitor-combination-therapy-in-type-2-diabetes
#2
REVIEW
André J Scheen
Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin)...
December 30, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28009472/effects-on-%C3%AE-and-%C3%AE-cell-function-of-sequentially-adding-empagliflozin-and-linagliptin-to-therapy-in-people-with-type-2-diabetes-previously-receiving-metformin-an-exploratory-mechanistic-study
#3
Thomas Forst, Alexander Falk, Grit Andersen, Annelie Fischer, Matthias M Weber, Stephan Voswinkel, Tim Heise, Christoph Kapitza, Leona Plum-Mörschel
AIMS: To investigate the effect of sequential treatment escalation with empagliflozin and linagliptin on laboratory markers of α- and β-cell function in people with type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin monotherapy. RESEARCH DESIGN AND METHODS: A total of 44 people with T2DM received 25 mg empagliflozin for a duration of 1 month in an open-label fashion (treatment period 1 [TP1]). Thereafter, they were randomized to a double-blind add-on therapy with linagliptin 5 mg or placebo (treatment period 2 [TP2]) for 1 additional month...
December 23, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28000562/synchronized-fast-spe-and-uflc-methods-for-the-analyses-of-eight-antidiabetic-drugs-in-human-plasma
#4
Imran Ali, Kamlesh Dutta, A K Jain
The number of the diabetic patients is increasing rapidly globally. The treatment of these patients is a complex phenomenon due to the use of the different drugs. The present article reports a synchronized fast SPE-UFLC separation of eight antidiabetic drugs in human plasma. The separated drugs include metformin HCl, vildagliptin, gliclazide, linagliptin, sitagliptin, pioglitazone, glimepiride and repaglinide. The column used was Sunshell C18 (150 x 4.6 mm, 2.6 µm) with mobile phase of acetate buffer (0.05% TEA in 0...
December 20, 2016: Combinatorial Chemistry & High Throughput Screening
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/27972163/network-meta-analysis-to-assess-the-relative-efficacy-and-safety-of-linagliptin-empagliflozin-and-the-fixed-dose-combination-of-empagliflozin-and-linagliptin-in-patients-with-type-2-diabetes-mellitus-t2dm
#7
I Daacke, S Kanters, K Thorlund, A Tebboth
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27942008/the-dpp4-inhibitor-linagliptin-protects-from-experimental-diabetic-retinopathy
#8
Nadine Dietrich, Matthias Kolibabka, Stephanie Busch, Petra Bugert, Ulrike Kaiser, Jihong Lin, Thomas Fleming, Michael Morcos, Thomas Klein, Andrea Schlotterer, Hans-Peter Hammes
BACKGROUND/AIMS: Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. METHODS: Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1...
2016: PloS One
https://www.readbyqxmd.com/read/27918671/dpp-4-inhibitor-treatment-in-chinese-type-2-diabetes-patients-a-meta-analysis
#9
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/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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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-1-and-pharmacokinetic-drug-drug-interaction-study-of-metformin-losartan-and-linagliptin-coadministered-with-dw1029m-in-healthy-volunteers
#20
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 DW1029M (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 randomized, open-label, 2-period, 2-treatment, multiple-dose, 2-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 hours on days 1 through 6 and a single dose on the morning of day 7...
October 14, 2016: Clinical Pharmacology in Drug Development
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