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Linagliptin

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https://www.readbyqxmd.com/read/28819835/efficacy-and-safety-of-linagliptin-in-2681-asian-patients-stratified-by-age-obesity-and-renal-function-a-pooled-analysis-of-randomized-clinical-trials
#1
Guang Ning, Tushar Bandgar, Uwe Hehnke, Jisoo Lee, Juliana C N Chan
INTRODUCTION: Asian patients with type 2 diabetes (T2D) are younger, leaner, and more likely to develop renal dysfunction than White populations. In this multiethnic analysis of data from phase 3 trials, we investigated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in Asians stratified by these subphenotypes. METHODS: Data from randomized, double-blind, placebo-controlled trials evaluating linagliptin (as monotherapy, add-on therapy to metformin ± sulfonylurea, combined with pioglitazone or added to insulin) were pooled with efficacy data from 11 randomized trials of at least 24 weeks and safety data from 15 trials of various durations...
August 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#2
Yanqing Zhang, Meifen Wu, Wynn Htun, Emily W Dong, Franck Mauvais-Jarvis, Vivian A Fonseca, Hongju Wu
Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771625/inhibition-of-dipeptidyl-peptidase-4-ameliorates-cardiac-ischemia-and-systolic-dysfunction-by-up-regulating-the-fgf-2-egr-1-pathway
#3
Masayoshi Suda, Ippei Shimizu, Yohko Yoshida, Yuka Hayashi, Ryutaro Ikegami, Goro Katsuumi, Takayuki Wakasugi, Yutaka Yoshida, Shujiro Okuda, Tomoyoshi Soga, Tohru Minamino
Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined. We found that linagliptin, a DPP-4 inhibitor, suppressed capillary rarefaction in the hearts of mice with dietary obesity. Metabolomic analysis performed with capillary electrophoresis/mass spectrometry (LC-MS/MS) showed that linagliptin promoted favorable metabolic remodeling in cardiac tissue, which was characterized by high levels of citrulline and creatine...
2017: PloS One
https://www.readbyqxmd.com/read/28719008/comparative-efficacy-and-safety-of-gemigliptin-versus-linagliptin-in-type-2-diabetes-patients-with-renal-impairment-a-40-week-extension-of-the-guard-randomized-study
#4
Sang Youb Han, Sun Ae Yoon, Byoung Geun Han, Sung Gyun Kim, Young-Il Jo, Kyung Hwan Jeong, Kook-Hwan Oh, Hyeong Cheon Park, Sun-Hee Park, Shin-Wook Kang, Ki-Ryang Na, Sun Woo Kang, Nam-Ho Kim, Younghwan Jang, Bogyeong Kim, Seonghye Shin, Dae Ryong Cha
AIMS: The present extension study evaluated the long-term safety and efficacy of gemigliptin during a 40-week follow-up period after a 12-week study. METHODS: The main study was a randomized, placebo-controlled, double-blinded, phase IIIb study in which 50 mg of gemigliptin (N = 66) or placebo (N = 66) was administered to patients with type 2 diabetes mellitus (T2DM) with moderate or severe renal impairment over a 12-week period. Patients with a glycated haemoglobin (HbA1c) level of 7-11% and an estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1...
July 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28715446/active-subfractions-of-abelmoschus-esculentus-substantially-prevent-free-fatty-acid-induced-%C3%AE-cell-apoptosis-via-inhibiting-dipeptidyl-peptidase-4
#5
Chien-Ning Huang, Chau-Jong Wang, Yi-Ju Lee, Chiung-Huei Peng
Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect...
2017: PloS One
https://www.readbyqxmd.com/read/28701284/cost-effectiveness-analysis-of-different-dipeptidyl-peptidase-4-inhibitor-drugs-for-treatment-of-type-2-diabetes-mellitus
#6
Maurílio de Souza Cazarim, Estael Luzia Coelho da Cruz-Cazarim, André de Oliveira Baldoni, Thais Bueno Enes Dos Santos, Paula Gonçalves de Souza, Ingrid de Almeida Silva, Roberta Niriam Reis Rodrigues, Alda Cristina Franco Correa Maia, Leonardo Régis Leira Pereira, Cristina Sanches
INTRODUCTION: Type 2 diabetes mellitus (T2DM) has burdened health systems in the world to the value of 500 billion dollars/year. Dipeptidyl peptidase 4 inhibitors (DPP-4 Inhibitors) have been strongly associated with spending on the treatment of T2DM by the courts in Brazil. The aim of this study was to estimate the most cost-effective DPP-4 Inhibitor for T2DM treatment. A pharmacoeconomic study of cost-effectiveness was performed in a medium-sized municipality in Minas Gerais state, Brazil...
July 3, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28683709/-linagliptin-induced-liver-toxicity
#7
Emma Bartolomé-García, Sira Sanz-Márquez, Montserrat Pérez-Encinas
No abstract text is available yet for this article.
July 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28671793/-gliptin-gliflozin-combination-for-treating-type-2-diabetes
#8
André J Scheen, Nicolas Paquot
Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycaemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach because the two drugs exert different and potentially complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin...
August 24, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28659588/the-dual-dpp4-inhibitor-and-gpr119-agonist-hbk001-regulates-glycemic-control-and-beta-cell-function-ex-and-in-vivo
#9
Yi Huan, Qian Jiang, Gang Li, Guoliang Bai, Tian Zhou, Shuainan Liu, Caina Li, Quan Liu, Sujuan Sun, Miaomiao Yang, Nan Guo, Xing Wang, Shusen Wang, Yaojuan Liu, Guanqiao Wang, Haihong Huang, Zhufang Shen
Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining β-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets...
June 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28653975/development-of-rp-hplc-stability-indicating-method-for-degradation-products-of-linagliptin-in-presence-of-metformin-hcl-by-applying-2-level-factorial-design-and-identification-of-impurity-vii-viii-and-ix-and-synthesis-of-impurity-vii
#10
Sushant B Jadhav, P Sunil Reddy, Kalyanaraman L Narayanan, Popatrao N Bhosale
The novel reverse phase-high performance liquid chromatography (RP-HPLC), stability indicating method was developed for determination of linagliptin (LGP) and its related substances in linagliptin and metformin HCl (MET HCl) tablets by implementing design of experiment to understand the critical method parameters and their relation with critical method attributes; to ensure robustness of the method. The separation of nine specified impurities was achieved with a Zorbax SB-Aq 250 × 4.6 mm, 5 µm column, using gradient elution and a detector wavelength of 225 nm, and validated in accordance with International Conference on Harmonization (ICH) guidelines and found to be accurate, precise, reproducible, robust, and specific...
June 27, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28636754/linagliptin-and-its-effects-on-hyperglycaemia-and-albuminuria-in-patients-with-type-2-diabetes-and-renal-dysfunction-the-randomized-marlina-t2d-trial
#11
Per-Henrik Groop, Mark E Cooper, Vlado Perkovic, Berthold Hocher, Keizo Kanasaki, Masakazu Haneda, Guntram Schernthaner, Kumar Sharma, Robert C Stanton, Robert Toto, Jessica Cescutti, Maud Gordat, Thomas Meinicke, Audrey Koitka-Weber, Sandra Thiemann, Maximilian von Eynatten
AIMS: The MARLINA-T2D study (ClinicalTrials.gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. METHODS: A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/mol), estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m(2) and urinary albumin-to-creatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks...
June 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28635331/network-meta-analysis-of-liraglutide-versus-dipeptidyl-peptidase-4-inhibitors-for-the-treatment-of-type-2-diabetes-in-japanese-patients
#12
Dieter Ayers, Steve Kanters, Rachel Goldgrub, Monica Hughes, Ryo Kato, Nana Kragh
AIMS: To determine the comparative efficacy and safety of liraglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors as antidiabetics for Japanese patients with uncontrolled type 2 diabetes (T2DM). METHODS AND MATERIALS: We searched for randomized controlled trials (RCTs) evaluating outcomes among Japanese adults with uncontrolled T2DM and including liraglutide or DPP-4 inhibitors up to August 2016. We extracted data on trial and patient characteristics, and the following outcomes: HbA1c, weight, patients meeting HbA1c <7%, patients experiencing hypoglycemic events, microalbuminuria, estimated glomerular filtration rate (eGFR) and creatinine...
July 19, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-nonalcoholic-steatohepatitis-and-liver-fibrosis
#13
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis, and increased cardiovascular mortality. Dipeptidyl peptidase-4 inhibitors (gliptins) are indirect glucagon-like peptide 1 agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
July 25, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28619389/the-promising-effect-of-linagliptin-and-or-indole-3-carbinol-on-experimentally-induced-polycystic-ovarian-syndrome
#14
Ahmed M Kabel, Aisha H Al-Shehri, Rehab A Al-Talhi, Maaly A Abd Elmaaboud
Polycystic ovarian syndrome (PCOS) is one of the most common medical conditions that lead to female infertility worldwide. The aim of this study was to assess the effect of linagliptin and/or indole-3-carbinol (I3C) on PCOS in female rats. Fifty female Wistar rats were randomly allocated into five equal groups: Control group; Letrozole-induced PCOS group; Letrozole + Linagliptin group; Letrozole + I3C group and Letrozole + Linagliptin + I3C group. Body weight, body mass index, Lee index and ovarian indices were determined...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28613952/healthcare-costs-among-adults-with-type-2-diabetes-initiating-saxagliptin-or-linagliptin-a-us-based-claims-analysis
#15
Amanda M Kong, Sepehr Farahbakhshian, Trudy Pendergraft, Matthew A Brouillette, Biswarup Mukherjee, David M Smith, John J Sheehan
OBJECTIVE: To compare healthcare costs of adults with type 2 diabetes (T2D) after initiation of saxagliptin or linagliptin, two antidiabetic medications in the dipeptidyl peptidase-4 inhibitor medication class. METHODS: Patients with T2D who were at least 18 years old and initiated saxagliptin or linagliptin (index date) between 1 June 2011 and 30 June 2014 were identified in the MarketScan Commercial and Medicare Supplemental Databases. All-cause healthcare costs and diabetes-related costs (T2D diagnosis on a medical claim and/or an antidiabetic medication claim) were measured in the 1 year follow-up period...
July 11, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28581818/effect-of-linagliptin-versus-metformin-on-glycemic-variability-in-patients-with-impaired-glucose-tolerance
#16
Tonatiuh González-Heredia, Diana M Hernández-Corona, Manuel González-Ortiz, Esperanza Martínez-Abundis
BACKGROUND: Impaired glucose tolerance (IGT) and glycemic variability may be associated with increased risk of micro- and macrovascular complications. The aim of this study was to assess the effect of linagliptin versus metformin on glycemic variability in patients with IGT. MATERIAL AND METHODS: A randomized, double-blind clinical trial with parallel groups was carried out in 16 adult patients with IGT, overweight or obesity. All patients signed an informed consent...
August 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28566414/linagliptin-associated-blistering-and-ulceration
#17
Cristina Psomadakis, Naima Shahzad, Jonathan Katz
We present the case of 60-year-old man with type 2 diabetes who developed blistering after two sequential exposures to linagliptin. Linagliptin is one of the dipeptidyl peptidase 4 (DPP-4) inhibitors, a group of oral hypoglycaemic agents used commonly for the treatment of type 2 diabetes. On the first exposure to linagliptin, he developed blisters on the hands which resolved after stopping the drug. After repeat exposure, he developed two large blisters on the left foot, which burst giving rise to secondary infection, requiring hospital admission for treatment...
May 31, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28476142/dipeptidyl-peptidase-4-dpp-4-inhibition-with-linagliptin-reduces-western-diet-induced-myocardial-traf3ip2-expression-inflammation-and-fibrosis-in-female-mice
#18
Annayya R Aroor, Javad Habibi, Hemanth Kumar Kandikattu, Mona Garro-Kacher, Brady Barron, Dongqing Chen, Melvin R Hayden, Adam Whaley-Connell, Shawn B Bender, Thomas Klein, Jaume Padilla, James R Sowers, Bysani Chandrasekar, Vincent G DeMarco
BACKGROUND: Diastolic dysfunction (DD), a hallmark of obesity and primary defect in heart failure with preserved ejection fraction, is a predictor of future cardiovascular events. We previously reported that linagliptin, a dipeptidyl peptidase-4 inhibitor, improved DD in Zucker Obese rats, a genetic model of obesity and hypertension. Here we investigated the cardioprotective effects of linagliptin on development of DD in western diet (WD)-fed mice, a clinically relevant model of overnutrition and activation of the renin-angiotensin-aldosterone system...
May 5, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28423178/head-to-head-comparison-of-structurally-unrelated-dipeptidyl-peptidase-4-inhibitors-in-the-setting-of-renal-ischemia-reperfusion-injury
#19
Christoph Reichetzeder, Karoline von Websky, Oleg Tsuprykov, Azadeh Mohagheghi Samarin, Luise Gabriele Falke, Sulistyo Emantoko Dwi Putra, Ahmed Abdallah Hasan, Viktoriia Antonenko, Caterina Curato, Jörg Rippmann, Thomas Klein, Berthold Hocher
BACKGROUND AND PURPOSE: Results regarding protective effects of dipeptidyl peptidase 4 (DPP4) inhibitors in renal ischaemia-reperfusion injury (IRI) are conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a model of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized male rats by renal artery clamping for 30 min. The sham group was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p.o. once daily on three consecutive days prior to IRI: linagliptin (1...
July 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28421983/comparative-study-between-multivariate-and-univariate-analysis-of-two-antidiabetic-combinations
#20
Maha F Abdel-Ghany, Omar Abdel-Aziz, Miriam F Ayad, Mariam M Tadros
New multivariate and univariate methods were developed for the analysis of two novel gliptin combinations by manipulating the zero-order and ratio spectra of empagliflozin and linagliptin in combination, with application on Glyxambi(®) tablets, and of alogliptin and pioglitazone in combination, with application on Oseni(®) tablets. Linearity ranges for chemometric approaches using principal component regression and partial least-squares were found to be 2–10, 2.5–12.5, 5–15, and 5–25 μg/mL for empagliflozin, linagliptin, alogliptin, and pioglitazone, respectively, whereas the respective linearity ranges for the spectrophotometric approaches were found to be 5–15, 2–12, 5–15, and 5–15 μg/mL...
April 18, 2017: Journal of AOAC International
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