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Sitagliptin AND Vildagliptin

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https://www.readbyqxmd.com/read/27895112/hepatic-dipeptidyl-peptidase-4-controls-pharmacokinetics-of-vildagliptin-in-vivo
#1
Mitsutoshi Asakura, Tatsuki Fukami, Miki Nakajima, Hideaki Fujii, Koichiro Atsuda, Tomoo Itoh, Ryoichi Fujiwara
The major metabolic pathway of vildagliptin, which is an inhibitor of dipeptidyl peptidase-4 (DPP-4), in humans is hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7. Our in vitro study previously demonstrated that DPP-4 itself greatly contributed to the hydrolysis of vildagliptin in mouse, rat, and human livers. To investigate whether hepatic DPP-4 contributes to the hydrolysis of vildagliptin in vivo, in the present study, we conducted in vivo pharmacokinetics studies of vildagliptin in mice co-administered with vildagliptin and sitagliptin, which is another DPP-4 inhibitor, and also in streptozotocin (STZ)-induced diabetic mice...
November 28, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27881129/impact-of-dipeptidyl-peptidase-4-inhibitors-on-serum-adiponectin-a-meta-analysis
#2
Xin Liu, Peng Men, Yuhui Wang, Suodi Zhai, George Liu
BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1)...
November 23, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27759084/vildagliptin-and-its-metabolite-m20-7-induce-the-expression-of-s100a8-and-s100a9-in-human-hepatoma-hepg2-and-leukemia-hl-60-cells
#3
Mitsutoshi Asakura, Fumika Karaki, Hideaki Fujii, Koichiro Atsuda, Tomoo Itoh, Ryoichi Fujiwara
Vildagliptin is a potent, orally active inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus. It has been reported that vildagliptin can cause hepatic dysfunction in patients. However, the molecular-mechanism of vildagliptin-induced liver dysfunction has not been elucidated. In this study, we employed an expression microarray to determine hepatic genes that were highly regulated by vildagliptin in mice. We found that pro-inflammatory S100 calcium-binding protein (S100) a8 and S100a9 were induced more than 5-fold by vildagliptin in the mouse liver...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27752788/the-place-of-dpp-4-inhibitors-in-the-treatment-algorithm-of-diabetes-type-2-a-systematic-review-of-cost-effectiveness-studies
#4
Alexandre Baptista, Inês Teixeira, Sónia Romano, António Vaz Carneiro, Julian Perelman
OBJECTIVE: To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. METHODS: Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list...
October 17, 2016: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
https://www.readbyqxmd.com/read/27665059/drug-drug-interactions-between-immunosuppressants-and-antidiabetic-drugs-in-the-treatment-of-post-transplant-diabetes-mellitus
#5
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/27642611/effectiveness-and-safety-of-newer-antidiabetic-medications-for-ramadan-fasting-diabetic-patients
#6
REVIEW
Ehab Mudher Mikhael
Hypoglycemia is the most common side effects for most glucose-lowering therapies. It constitutes a serious risk that faces diabetic patients who fast during Ramadan (the 9th month in the Islamic calendar). New glucose-lowering classes like dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are efficacious in controlling blood glucose level with less tendency to induce hypoglycemia and thus may constitute a good choice for diabetic patients during Ramadan...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27640062/insulin-monotherapy-compared-with-the-addition-of-oral-glucose-lowering-agents-to-insulin-for-people-with-type-2-diabetes-already-on-insulin-therapy-and-inadequate-glycaemic-control
#7
Rimke C Vos, Mariëlle Jp van Avendonk, Hanneke Jansen, Alexander N Goudswaard, Maureen van den Donk, Kees Gorter, Anneloes Kerssen, Guy Ehm Rutten
BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control...
September 18, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27519975/assessment-of-the-price-volume-agreement-program-in-south-korea
#8
Euna Han, Sun-Young Park, Eui-Kyung Lee
The Price-Volume Agreement Program (PVAP) was promulgated in 2007 in South Korea as the first attempt to adjust drug pricing according to total consumption in order to contain drug expenditure. This study was designed to assess the impact of the PVAP on diabetes drug expenditure for a period of a 10-year period (2003-2012) using claims data from the National Health Insurance Service. We estimated a multilevel mixed-effects linear regression model by comparing the level of total monthly diabetes drug expenditure for drugs subject to PVAP and existing drugs after adjusting the average differences in drug expenditure before and after the PVAP...
August 2, 2016: Health Policy
https://www.readbyqxmd.com/read/27516879/an-updated-systematic-review-and-meta-analysis-on-the-efficacy-and-tolerability-of-dipeptidyl-peptidase-4-inhibitors-in-patients-with-type-2-diabetes-with-moderate-to-severe-chronic-kidney-disease
#9
Devada Singh-Franco, Catherine Harrington, Eglis Tellez-Corrales
OBJECTIVE: This updated meta-analysis determines the effect of dipeptidyl peptidase-4 inhibitors on glycemic and tolerability outcomes in patients with type 2 diabetes mellitus and chronic kidney disease with glomerular filtration rate of ⩽60 mL/min or on dialysis. METHODS: In all, 14 citations were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. RESULTS: There were 2261 participants, 49-79 years of age, 49% men and 44% Caucasians...
2016: SAGE Open Medicine
https://www.readbyqxmd.com/read/27512877/efficacy-of-different-dipeptidyl-peptidase-4-dpp-4-inhibitors-on-metabolic-parameters-in-patients-with-type-2-diabetes-undergoing-dialysis
#10
Se Hee Park, Joo Young Nam, Eugene Han, Yong-Ho Lee, Byung-Wan Lee, Beom Seok Kim, Bong-Soo Cha, Chul Sik Kim, Eun Seok Kang
Hyperglycemia is associated with increased mortality and morbidity in patients with type 2 diabetes mellitus (T2DM) who are undergoing dialysis. Although dipeptidyl peptidase-4 (DPP-4) inhibitors have been widely used in end-stage renal disease (ESRD) patients with T2DM, there are few studies on their efficacy in this population. We studied the effect of 3 different DPP-4 inhibitors on metabolic parameters in ESRD patients with T2DM.Two hundred ESRD patients with T2DM who were treated with DPP-4 inhibitors (sitagliptin, vildagliptin, or linagliptin) were enrolled and analyzed retrospectively...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27502495/systematic-literature-review-of-dpp-4-inhibitors-in-patients-with-type-2-diabetes-mellitus-and-renal-impairment
#11
REVIEW
Merlin C Thomas, Päivi M Paldánius, Rajeev Ayyagari, Siew Hwa Ong, Per-Henrik Groop
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off, June 2015) to identify ≥12-week, randomized, placebo-controlled trials on DPP-4 inhibitors in ≥50 patients with T2DM and RI...
September 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27491279/demographic-and-clinical-characteristics-of-patients-with-type-2-diabetes-mellitus-initiating-dipeptidyl-peptidase-4-inhibitors-a-retrospective-study-of-uk-general-practice
#12
Abigail Tebboth, Sally Lee, Anna Scowcroft, Paula Bingham-Gardiner, Will Spencer, John Bolodeoku, Syed Wasi Hassan
PURPOSE: The majority of people with type 2 diabetes mellitus (T2DM) will develop chronic kidney disease in their lifetime. Because most dipeptidyl peptidase (DPP)-4 inhibitors require dose adjustment in patients with T2DM and renal impairment, we aimed to understand how these treatments are prescribed in UK clinical practice, and to determine whether recommended dose adjustments are being made at initial prescription. METHODS: This retrospective, descriptive cohort study analyzed data from the Clinical Practice Research Datalink (CPRD)...
August 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27389437/no-increased-risk-of-hospitalization-for-heart-failure-for-patients-treated-with-dipeptidyl-peptidase-4-inhibitors-in-taiwan
#13
Chia-Hsuin Chang, Yi-Cheng Chang, Jou-Wei Lin, James L Caffrey, Li-Chiu Wu, Mei-Shu Lai, Lee-Ming Chuang
BACKGROUND: Saxagliptin has been reported to be associated with an increased risk of hospitalization for heart failure (HF). The objective of this study was to test whether the increased risk is drug specific or a class effect for dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: Diabetic patients prescribed sitagliptin, saxagliptin, and vildagliptin between 2011 and 2013 were identified from Taiwan's National Health Insurance (NHI) claims database. The outcome of interest was the first hospitalization for HF...
October 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27321385/comparative-effects-of-vildagliptin-and-sitagliptin-determined-by-continuous-glucose-monitoring-in-patients-with-type-2-diabetes-mellitus
#14
Naohide Koyanagawa, Hideaki Miyoshi, Kota Ono, Akinobu Nakamura, Kyu Yong Cho, Kohei Yamamoto, Yoshinari Takano, Midori Dan-Noura, Tatsuya Atsumi
The dipeptidyl peptidase-4 inhibitors vildagliptin and sitagliptin are effective in treating patients with type 2 diabetes mellitus. Patients receiving standard doses of sitagliptin plus insulin may require increased doses of sitagliptin or switching to vildagliptin to improve blood glucose control. This study compared the effects of increasing sitagliptin and switching to vildagliptin in type 2 diabetes patients receiving standard doses of sitagliptin plus insulin. This prospective, randomized, parallel-group comparison trial enrolled 33 type 2 diabetes patients receiving 50 mg sitagliptin once daily plus insulin...
August 31, 2016: Endocrine Journal
https://www.readbyqxmd.com/read/27300579/feed-back-suppression-of-meal-induced-glp-1-secretion-mediated-through-elevations-in-intact-glp-1-caused-by-dpp-4-inhibition-a-randomized-prospective-comparison-of-sitagliptin-and-vildagliptin-treatment
#15
Oleg Baranov, Melanie Kahle, Carolyn F Deacon, Jens J Holst, Michael A Nauck
BACKGROUND: The present study was designed to directly compare clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L-cell feedback inhibition induced by DPP-4 inhibition. PATIENTS/METHODS: 24 patients (12 diet/exercise, 12 on metformin) were treated, in randomized order, for 7-9 days , with either vildagliptin (50 mg b.i.d. = 100 mg/d), sitagliptin (100 mg q.d. in those on diet, 50 mg b...
June 14, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27298192/pharmacological-profiles-of-gemigliptin-lc15-0444-a-novel-dipeptidyl-peptidase-4-inhibitor-in-vitro-and-in-vivo
#16
Sung-Ho Kim, Eunsoo Jung, Min Kyung Yoon, O Hwan Kwon, Dal-Mi Hwang, Dong-Wook Kim, Junghyun Kim, Sun-Mee Lee, Hyeon Joo Yim
Gemigliptin, a novel dipeptidyl peptidase (DPP)-4 inhibitor, is approved for use as a monotherapy or in combination therapy to treat hyperglycemia in patients with type 2 diabetes mellitus. In this study, we investigated the pharmacological profiles of gemigliptin in vitro and in vivo and compared them to those of the other DPP-4 inhibitors. Gemigliptin was a reversible and competitive inhibitor with a Ki value of 7.25±0.67nM. Similar potency was shown in plasma from humans, rats, dogs, and monkeys. The kinetics of DPP-4 inhibition by gemigliptin was characterized by a fast association and a slow dissociation rate compared to sitagliptin (fast on and fast off rate) or vildagliptin (slow on and slow off rate)...
October 5, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27249660/clinical-and-genetic-predictors-of-dipeptidyl-peptidase-4-inhibitor-treatment-response-in-type-2-diabetes-mellitus
#17
Jazlina Liza Jamaluddin, Hasniza Zaman Huri, Shireene Ratna Vethakkan
AIM: To determine the clinical and genetic predictors of the dipeptidyl peptidase-4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients. PATIENTS & METHODS: DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay. RESULTS: Patients with triglyceride levels less than 1...
June 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27105869/dipeptidyl-peptidase-4-inhibition-in-chronic-kidney-disease-and-potential-for-protection-against-diabetes-related-renal-injury
#18
REVIEW
G Penno, M Garofolo, S Del Prato
AIMS: Type 2 diabetes mellitus (T2DM) is associated with a high risk of chronic kidney disease (CKD). About 20% of patients with T2DM have CKD of stage ≥ 3; up to 40% have some degree of CKD. Beyond targeting all renal risk factors together, renin-angiotensin-aldosterone system blockers are to date the only effective mainstay for the treatment of diabetic kidney disease (DKD). Indeed, several potentially nephroprotective agents have been in use, which have been unsuccessful. Some glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i), have shown promising results...
May 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27067162/dipeptidyl-peptidase-4-inhibitors-and-heart-failure-analysis-of-spontaneous-reports-submitted-to-the-fda-adverse-event-reporting-system
#19
E Raschi, E Poluzzi, A Koci, I C Antonazzo, G Marchesini, F De Ponti
BACKGROUND AND AIMS: We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). METHODS: FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query "Cardiac failure". Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders...
May 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27048342/effect-of-dipeptidyl-peptidase-4-inhibitors-on-plasma-adiponectin-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#20
Amirhossein Sahebkar, Valentina Ponzo, Simona Bo
BACKGROUND/OBJECTIVES: The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on plasma concentrations of adiponectin, a fat-derived hormone with anti-atherogenic and anti-inflammatory properties, is uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate this association in humans. METHODS: RCTs investigating the impact of DPP-4 inhibitors on plasma adiponectin concentrations were identified after searching PubMed-Medline, SCOPUS, and Google Scholar databases (up to February 2015)...
2016: Current Medicinal Chemistry
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