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sitagliptin

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https://www.readbyqxmd.com/read/28423178/head-to-head-comparison-of-structurally-unrelated-dpp4-inhibitors-in-the-setting-of-renal-ischemia-reperfusion-injury
#1
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 Rippman, Thomas Klein, Berthold Hocher
BACKGROUND AND PURPOSE: Results regarding protective effects of DPP4 inhibitors in renal ischemia-reperfusion-injury (IRI) are conflicting. The current study performed a head-to-head comparison of structurally unrelated DPP4 inhibitors in the setting of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized male rats by renal artery clamping for 30 minutes. The sham group was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p...
April 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28420697/erratum-sitagliptin-attenuates-the-progression-of-carotid-intima-media-thickening-in-insulin-treated-patients-with-type-2-diabetes-the-sitagliptin-preventive-study-of-intima-media-thickness-evaluation-spike-a-randomized-controlled-trial-diabetes-care-2016-39
#2
Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Tomio Onuma, Nobuichi Kuribayashi, Takeshi Osonoi, Hideaki Kaneto, Keisuke Kosugi, Yutaka Umayahara, Tsunehiko Yamamoto, Kazunari Matsumoto, Hiroki Yokoyama, Mamiko Tsugawa, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
No abstract text is available yet for this article.
April 18, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#3
REVIEW
André J Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced...
March 25, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28385659/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-sitagliptin-as-an-add-on-to-metformin-thiazolidinediones-or-both-in-patients-with-type-2-diabetes-sustain-2-a-56-week-double-blind-phase-3a-randomised-trial
#4
Bo Ahrén, Luis Masmiquel, Harish Kumar, Mehmet Sargin, Julie Derving Karsbøl, Sanja Hald Jacobsen, Francis Chow
BACKGROUND: Semaglutide is a novel glucagon-like peptide-1 (GLP-1) analogue, suitable for once-weekly subcutaneous administration, in development for treatment of type 2 diabetes. We assessed the efficacy and safety of semaglutide versus the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin, thiazolidinediones, or both. METHODS: We did a 56-week, phase 3a, randomised, double-blind, double-dummy, active-controlled, parallel-group, multinational, multicentre trial (SUSTAIN 2) at 128 sites in 18 countries...
April 3, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28382499/sitagliptin-exerts-anti-apoptotic-effect-in-nephrotoxicity-induced-by-cisplatin-in-rats
#5
Rehab S Abdelrahman
Sitagliptin is a selective inhibitor of dipeptidylpeptidase-4 enzyme used for the management of diabetes mellitus type II. The anti-inflammatory, antioxidant, and anti-apoptotic properties of sitagliptin were documented. This study was designed to explore the effect of sitagliptin (10 mg/kg, orally) on nephrotoxicity induced by cisplatin (7 mg/kg, i.p.) in Sprague-Dawley rats. Nephrotoxicity of cisplatin was manifested by elevation in renal somatic index, proteinuria, blood urea nitrogen, creatinine in serum, lactate dehydrogenase, kidney malondialdehyde, NF-κB, Bax, and annexin V...
April 5, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28375099/beneficial-effects-of-sitagliptin-and-metformin-in-non-diabetic-hypertensive-and-dyslipidemic-patients
#6
Mazhar Hussain, Moazzam Ali Atif, Muhammad Bilal R Ghafoor
Obesity, dyslipidemia and hypertension are major risk factors for cardiovascular disease and its associated complications. To evaluate the beneficial effects of sitagliptin and metformin in non-diabetic dyslipidemic and hypertensive patients. A prospective randomized clinical trial was conducted on 70 newly diagnosed dyslipidemic patients with BMI > 25 and blood pressure > 130/80 at outpatient clinic of medical unit-1 of Sheikh Medical College/Hospital, Rahim Yar Khan. They were divided in to three groups each containing 35 patients; First group served as a healthy control while second and third study groups were given tablet sitagliptin 50mg and tab metformin 850mg respectively twice a day for twelve weeks...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28372289/dpp4-regulates-the-inflammatory-response-in-a-rat-model-of-febrile-seizures
#7
Qi Sun, Yusong Zhang, Jie Huang, Fang Yu, Jian Xu, Biwen Peng, Wanhong Liu, Song Han, Jun Yin, Xiaohua He
Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28371155/treatment-with-ly2409021-a-glucagon-receptor-antagonist-increases-liver-fat-in-patients-with-type-2-diabetes
#8
Cristina B Guzman, Xiaotian Michelle Zhang, Rong Liu, Arie Regev, Sudha Shankar, Parag Garhyan, Sreekumar G Pillai, Christof Kazda, Naga Chalasani, Thomas A Hardy
AIMS: Glucagon receptor antagonists (GRAs) represent a clinically validated new class of molecules for the treatment of type 2 diabetes (T2D) however these molecules are associated with increases in hepatic aminotransferases. We evaluated whether treatment with LY2409021, a novel, selective GRA, is associated with changes in hepatic fat and other safety parameters related to the benefit-risk profile for chronic use. MATERIALS AND METHODS: Safety and efficacy were assessed in patients with T2D taking metformin and sulfonylurea randomized to LY2409021 20mg (N=65), placebo (N=68), or sitagliptin 100mg (N=41)...
March 31, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28368384/glp-1-acts-on-habenular-avoidance-circuits-to-control-nicotine-intake
#9
Luis M Tuesta, Zuxin Chen, Alexander Duncan, Christie D Fowler, Masago Ishikawa, Brian R Lee, Xin-An Liu, Qun Lu, Michael Cameron, Matthew R Hayes, Theodore M Kamenecka, Matthew Pletcher, Paul J Kenny
Tobacco smokers titrate their nicotine intake to avoid its noxious effects, sensitivity to which may influence vulnerability to tobacco dependence, yet mechanisms of nicotine avoidance are poorly understood. Here we show that nicotine activates glucagon-like peptide-1 (GLP-1) neurons in the nucleus tractus solitarius (NTS). The antidiabetic drugs sitagliptin and exenatide, which inhibit GLP-1 breakdown and stimulate GLP-1 receptors, respectively, decreased nicotine intake in mice. Chemogenetic activation of GLP-1 neurons in NTS similarly decreased nicotine intake...
April 3, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28358275/demographic-and-clinical-profiles-of-type-2-diabetes-mellitus-patients-initiating-sitagliptin-in-the-real-world-setting
#10
Manjiri Pawaskar, Jinan Liu, Swapnil Rajpathak, Kristy Iglay, Samuel S Engel, Hakima Hannachi
OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been used for the management of type 2 diabetes (T2D) for over a decade; however, there is a limited understanding of the evolution of their use in the real world setting over this time period. This study evaluated the demographics, and clinical characteristics of patients initiating sitagliptin over a 10-year period in the United States. RESEARCH DESIGN AND METHODS: Quintiles electronic medical records database was used to identify adults with a new prescription of sitagliptin over two 5-year time periods: 2006-2010 (n = 57,604), and 2011-2015 (n = 147,326)...
March 30, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28355570/pancreatic-%C3%AE-cell-derived-glucagon-related-peptides-are-required-for-%C3%AE-cell-adaptation-and-glucose-homeostasis
#11
Shuyang Traub, Daniel T Meier, Friederike Schulze, Erez Dror, Thierry M Nordmann, Nicole Goetz, Norina Koch, Elise Dalmas, Marc Stawiski, Valmir Makshana, Fabrizio Thorel, Pedro L Herrera, Marianne Böni-Schnetzler, Marc Y Donath
Pancreatic α cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects of locally derived insulin secretagogues on β cell function and glucose homeostasis using mice with α cell ablation and with α cell-specific GLP-1 deficiency. Normally, intestinal GLP-1 compensates for the lack of α cell-derived GLP-1. However, upon aging and metabolic stress, glucose tolerance is impaired...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28349708/use-of-sitagliptin-with-closed-loop-technology-to-decrease-postprandial-blood-glucose-in-type-1-diabetes
#12
Lisa J Underland, Jeniece Trast Ilkowitz, Ranjitha Katikaneni, Amy Dowd, Rubina A Heptulla
BACKGROUND: Postprandial hyperglycemia poses a challenge to closed-loop systems. Dipeptidyl peptidase-4 (DPP-4) inhibitors, like sitagliptin, reduce postprandial glucose concentrations in patients with type 2 diabetes. The objective of this study was to assess sitagliptin's role in type 1 diabetes (T1DM) as an adjunct therapy in reducing postprandial blood glucose with an insulin-only closed-loop system. METHODS: This was a randomized, double-blinded, placebo controlled, crossover design trial...
March 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28345162/reduction-of-postprandial-glucose-by-lixisenatide-versus-sitagliptin-in-japanese-patients-with-type-2-diabetes-on-background-insulin-glargine-a-randomised-phase-4-study
#13
Yuichiro Yamada, Masayuki Senda, Yusuke Naito, Masahiro Tamura, Daisuke Watanabe, Yujin Shuto, Yoshihisa Urita
AIM: To evaluate the pharmacodynamics of adjunctive lixisenatide once daily versus sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100. METHODS: This multicentre, open-label, phase 4 study (NCT02200991) randomly assigned 136 patients to either lixisenatide once-daily subcutaneous injection (10 µg initially increased weekly by 5 µg up to 20 µg) or once-daily oral sitagliptin (50 mg dose). The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration-time curve [AUC0:00-4:00h ]) from baseline to Day 29...
March 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28334048/hepatoprotective-effect-of-sitagliptin-against-methotrexate-induced-liver-toxicity
#14
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
https://www.readbyqxmd.com/read/28331117/comparison-between-effectiveness-of-100-mg-day-sitagliptin-and-a-switch-to-mitiglinide-calcium-hydrate-voglibose-from-50-mg-day-sitagliptin-in-patients-with-type-2-diabetes
#15
Tadashi Arao, Yosuke Okada, Keiichi Torimoto, Kei Sugai, Takashi Otsuka, Akira Kurozumi, Yoshiya Tanaka
We analyzed the effects of 100 mg/day sitagliptin and a switch to mitiglinide calcium hydrate/voglibose compound tablets (MIT/VOG) in patients with type 2 diabetes mellitus (T2DM) treated with 50 mg/day sitagliptin. Five patients with T2DM treated with 50 mg/day sitagliptin and hemoglobin A1c (HbA1c) of ≥6.5% were switched to MIT/VOG, or the dose of sitagliptin was increased to 100 mg/day. The effects of the changes in therapy were compared in a crossover fashion by continuous glucose monitoring. The primary endpoint was mean amplitude of glycemic excursions (MAGE), and the secondary end points were 24-hour mean blood glucose level and mean blood glucose level from 0:00 a...
2017: Journal of UOEH
https://www.readbyqxmd.com/read/28329747/influence-of-dipeptidyl-peptidase-iv-inhibitor-sitagliptin-on-extracellular-signal-regulated-kinases-1-2-signaling-in-rats-with-diabetic-nephropathy
#16
Xiaojun Ren, Gaohong Liu, Yanhong Wang, Wan Zhang, Fuping Xue, Rongshan Li, Weimin Yu
The protective effects of sitagliptin on the kidneys of rats with diabetic nephropathy (DN) and its influence on extracellular signal-regulated kinases 1/2 (ERK1/2) signaling were investigated. Male Wistar rats (n = 40) were randomly assigned to normal control, DN, low-dose sitagliptin intervention (ST1), or high-dose sitagliptin intervention (ST2) groups. Animals were euthanized after a 16-week treatment, and blood glucose (BG), glycosylated hemoglobin (HbA1c), urinary albumin excretion rate (AER), serum creatinine (Scr), creatinine clearance rate (Ccr), active glucagon-like peptide-1 (GLP-1) levels, kidney hypertrophy index, and renal pathohistology were determined...
March 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-following-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#17
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFA) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323942/incretin-therapies-do-not-expand-%C3%AE-cell-mass-or-alter-pancreatic-histology-in-young-male-mice
#18
Aaron R Cox, Carol J Lam, Matthew M Rankin, Jacqueline S Rios, Julia Chavez, Claire W Bonnyman, Kourtney B King, Roger A Wells, Deepti Anthony, Justin X Tu, Jenny J Kim, Changhong Li, Jake A Kushner
The impact of incretins upon pancreatic β-cell expansion remains extremely controversial. Multiple studies indicate that incretin-based therapies can increase β-cell proliferation, and incretins have been hypothesized to expand β-cell mass. However, considerable disagreement exists on whether incretins actually increase β-cell mass. Moreover, some reports indicate that incretins may cause metaplastic changes in pancreatic histology. To resolve these questions we treated a large cohort of mice with incretin-based therapies and carried out a rigorous analysis of β-cell turnover and pancreatic histology using high-throughput imaging...
March 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322746/truncation-of-cxcl12-by-cd26-reduces-its-cxc-chemokine-receptor-4-and-atypical-chemokine-receptor-3-dependent-activity-on-endothelial-cells-and-lymphocytes
#19
Rik Janssens, Anneleen Mortier, Daiane Boff, Pieter Ruytinx, Mieke Gouwy, Bo Vantilt, Olav Larsen, Viktorija Daugvilaite, Mette M Rosenkilde, Marc Parmentier, Sam Noppen, Sandra Liekens, Jo Van Damme, Sofie Struyf, Mauro M Teixeira, Flávio A Amaral, Paul Proost
The chemokine CXCL12 or stromal cell-derived factor 1/SDF-1 attracts hematopoietic progenitor cells and mature leukocytes through the G protein-coupled CXC chemokine receptor 4 (CXCR4). In addition, it interacts with atypical chemokine receptor 3 (ACKR3 or CXCR7) and glycosaminoglycans. CXCL12 activity is regulated through posttranslational cleavage by CD26/dipeptidyl peptidase 4 that removes two NH2-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells...
March 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28321057/the-glucose-lowering-efficacy-of-sitagliptin-in-obese-japanese-patients-with-type-2-diabetes
#20
Ryo Kodera, Kenichi Shikata, Akihiko Nakamura, Satoru Okazaki, Ryo Nagase, Tatsuaki Nakatou, Shigeru Haisa, Kazuyuki Hida, Katsuhiro Miyashita, Hirofumi Makino
Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors are the most frequently prescribed oral hypoglycemic agents in Japan. Although a relationship between the efficacy of DPP-4 inhibitors and the body mass index (BMI) has been reported, this relationship is controversial. We investigated whether the BMI value affects the glucose-lowering efficacy of sitagliptin in obese Japanese patients with type 2 diabetes. Methods One hundred sixty-two outpatients with inadequate glycemic control were divided into four groups based on their baseline BMI values...
2017: Internal Medicine
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