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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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 N-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells...
March 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28321057/the-glucose-lowering-efficacy-of-sitagliptin-in-obese-japanese-patients-with-type-2-diabetes
#8
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
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#9
Bilin Xu, Tian Shen, Lin Chen, Juan Xia, Cuiping Zhang, Hongping Wang, Ming Yu, Tao Lei
BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks...
March 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28294488/the-efficacy-and-safety-of-sitagliptin-as-compared-with-glimepiride-in-japanese-patients-aged-60-years-or-older-with-type-2-diabetes-mellitus-start-j-trial
#10
Yasuo Terauchi, Yuichiro Yamada, Hitoshi Ishida, Mitsuru Ohsugi, Masafumi Kitaoka, Jo Satoh, Daisuke Yabe, Nobuyuki Shihara, Yutaka Seino
Non structured abstract To evaluate the efficacy and safety of sitagliptin administered to elderly patients with type 2 diabetes mellitus (T2DM) for one year as compared with glimepiride. Patients aged ≥ 60 years with T2DM and inadequately controlled blood glucose were randomly assigned to sitagliptin 50 mg qd or glimepiride 0.5 mg qd for 52 weeks. The primary efficacy endpoint was the change in HbA1c from baseline to Week 52. Secondary efficacy endpoints included self-monitored blood glucose (SMBG) and weight...
March 9, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#11
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
April 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28283565/assessment-of-pancreas-safety-in-the-development-program-of-once-weekly-glp-1-receptor-agonist-dulaglutide
#12
Michael A Nauck, Jean-Louis Frossard, Jamie S Barkin, Greg Anglin, Ingrid E Hensley, Kristine D Harper, Zvonko Milicevic
OBJECTIVE: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials. RESEARCH DESIGN AND METHODS: A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks...
March 10, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28276830/bariatric-surgery-time-to-replace-with-glp-1
#13
Dominic-Luc Webb, Niclas Abrahamsson, Magnus Sundbom, Per M Hellström
Obesity with a body mass index (BMI) over 30 kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass...
February 24, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28275958/comparative-effectiveness-of-adding-alogliptin-to-metformin-plus-sulfonylurea-with-other-dpp-4-inhibitors-in-type-2-diabetes-a-systematic-review-and-network-meta-analysis
#14
REVIEW
Stephen Kay, Amanda Strickson, Jorge Puelles, Ross Selby, Eugene Benson, Keith Tolley
INTRODUCTION: Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), approved for the treatment of type 2 diabetes mellitus (T2DM). There currently exists no comparative data to support the use of alogliptin in combination with metformin (met) and sulfonylurea (SU). A decision-focused network meta-analysis (NMA) was performed to compare the relative efficacy and safety of alogliptin 25 mg once daily to other DPP-4 inhibitors as part of a triple therapy regimen for patients inadequately controlled on metformin and SU dual therapy...
March 8, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28271251/efficacy-and-safety-of-metformin-and-sitagliptin-based-triple-antihyperglycemic-therapy-strategy-a-multicenter-randomized-controlled-non-inferiority-clinical-trial
#15
Wen Xu, Yiming Mu, Jiajun Zhao, Dalong Zhu, Qiuhe Ji, Zhiguang Zhou, Bin Yao, Anhua Mao, Samuel S Engel, Bin Zhao, Yan Bi, Longyi Zeng, Xingwu Ran, Juming Lu, Linong Ji, Wenying Yang, Weiping Jia, Jianping Weng
Despite the current guideline's recommendation of a timely stepwise intensification therapy, the "clinical inertia", termed as the delayed treatment intensification, commonly exists in the real world, which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy. In this clinical trial performed in 237 centers in China, 5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks...
February 7, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28260702/effects-of-50-mg-vildagliptin-twice-daily-vs-50-mg-sitagliptin-once-daily-on-blood-glucose-fluctuations-evaluated-by-long-term-self-monitoring-of-blood-glucose
#16
Hiroshi Nomoto, Kimihiko Kimachi, Hideaki Miyoshi, Hiraku Kameda, Kyu Yong Cho, Akinobu Nakamura, So Nagai, Takuma Kondo, Tatsuya Atsumi
To date, several clinical trials have compared differences in glucose fluctuation observed with dipeptidyl peptidase-4 inhibitor treatment in patients with type 2 diabetes mellitus. However, most patients were assessed for limited periods or during hospitalization. The aim of the present study was to evaluate the effects of switching from sitagliptin to vildagliptin, or vice versa, on 12-week glucose fluctuations using self-monitoring of blood glucose in the standard care setting. We conducted a multicenter, prospective, open-label controlled trial in Japanese patients with type 2 diabetes...
March 3, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28258522/sitagliptin-and-liraglutide-reversed-nigrostriatal-degeneration-of-rodent-brain-in-rotenone-induced-parkinson-s-disease
#17
Ghada A Badawi, Mai A Abd El Fattah, Hala F Zaki, Moushira I El Sayed
The present study investigated the possible relationship between pro-inflammatory cytokines and programmed nigral neuronal death in rotenone model of Parkinson's disease (PD). Sitagliptin and liraglutide efficacy to inhibit the inflammatory-apoptotic degenerative process were investigated, too. The experimental PD were induced in male albino rats by ten subcutaneously injections of rotenone (3 mg/kg/day, s.c). All treatment drugs were administered for 16 days after induction of Parkinson rat's model. Sitagliptin and liraglutide were administered in three different dose levels (10-20-30 mg/kg, p...
March 4, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28250768/the-effect-of-sitagliptin-on-the-regression-of-carotid-intima-media-thickening-in-patients-with-type-2-diabetes-mellitus-a-post-hoc-analysis-of-the-sitagliptin-preventive-study-of-intima-media-thickness-evaluation
#18
Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
Background. The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT) in insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods. This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28239939/combining-the-gpr40-agonist-fasiglifam-with-sitagliptin-improves-glycemic-control-in-patients-with-type-2-diabetes-with-or-without-metformin-a-randomized-12-week-trial
#19
Xuejun V Peng, John F Marcinak, Marsha G Raanan, Charlie Cao
AIMS: To evaluate the efficacy and safety of fasiglifam, an orally active G protein-coupled receptor 40 agonist, in combination with the dipeptidyl peptidase-4 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet/exercise (± metformin). METHODS: In this randomized, double-blind, phase II study, 368 patients received once-daily placebo, sitagliptin 100 mg, fasiglifam 25 or 50 mg, or the combination of sitagliptin 100 mg plus fasiglifam 25 or 50 mg...
February 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28238556/bile-acid-sequestrants-for-glycemic-control-in-patients-with-type-2-diabetes-a-systematic-review-with-meta-analysis-of-randomized-controlled-trials
#20
Morten Hansen, David P Sonne, Kristian H Mikkelsen, Lise Lotte Gluud, Tina Vilsbøll, Filip K Knop
AIM: To evaluate the effects of bile acid sequestrants (BASs) versus placebo, no intervention or active comparators on glycemic control in type 2 diabetes. METHODS: Data were retrieved and a systematic review with meta-analyses was performed. We evaluated bias control and subgroup and sensitivity analyses were performed to evaluate heterogeneity and bias. RESULTS: We included 17 trials with a total of 2950 patients randomized to BASs (colesevelam or colestimide) versus placebo, no intervention, statins or sitagliptin...
January 24, 2017: Journal of Diabetes and its Complications
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