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https://www.readbyqxmd.com/read/28213841/sitagliptin-down-regulates-retinol-binding-protein-4-and-reduces-insulin-resistance-in-gestational-diabetes-mellitus-a-randomized-and-double-blind-trial
#1
Xia Sun, Zhendong Zhang, Hui Ning, Hong Sun, Xianghong Ji
Gestational diabetes mellitus (GDM) is a condition that affects increasing number of pregnant women worldwide. Sitagliptin was reported to alleviate symptoms of type 2 diabetes mellitus by reducing serum levels of retinol-binding protein 4 (RBP-4). We investigated the effectiveness of sitagliptin on insulin sensitivity parameters in GDM patients. Pregnant GDM women in the 2nd trimester were recruited for this study. Participants were then assigned randomly to sitagliptin treatment group or placebo treatment group, and administered sitagliptin or placebo daily for 16 weeks...
February 17, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28205322/efficacy-and-safety-of-autoinjected-exenatide-once-weekly-suspension-versus-sitagliptin-or-placebo-with-metformin-in-patients-with-type-2-diabetes-the-duration-neo-2-randomized-clinical-study
#2
Kishore M Gadde, Marion L Vetter, Nayyar Iqbal, Elise Hardy, Peter Öhman
AIMS: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo. MATERIALS AND METHODS: In this open-label, multicenter study of patients with type 2 diabetes who had suboptimal glycemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28197977/interpreting-cardiovascular-endpoints-in-trials-of-antihyperglycemic-drugs
#3
REVIEW
Himika Chawla, Nikhil Tandon
In view of the significant cardiovascular (CV) morbidity and mortality in patients with type 2 diabetes mellitus, and concerns raised about the CV safety of some glucose-lowering drugs, the US Food and Drug Administration (FDA) issued guidance for the industry in 2008 to demonstrate CV safety for the approval of all new antihyperglycemic drugs. Seven randomized controlled trials involving around 60,000 participants have been completed so far and have demonstrated the CV safety of dipeptidyl peptidase 4 inhibitors (saxagliptin, alogliptin and sitagliptin), glucagon-like peptide-1 receptor agonists (lixisenatide, liraglutide and semaglutide) and a sodium-glucose co-transporter 2 inhibitor (empagliflozin) in patients with type 2 diabetes...
February 14, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28188238/vmp1-related-autophagy-induced-by-fructose-rich-diet-in%C3%A2-%C3%AE-cells-it-s-prevention-by-incretins
#4
Bárbara Maiztegui, Verónica Boggio, Carolina Lisi Román, Luis Emilio Flores, Héctor Del Zotto, Alejandro Ropolo, Daniel Grasso, María Inés Vaccaro, Juan José Gagliardino
Aim : To demonstrate the role of autophagy and incretins on fructose-induced alteration in β-cell mass and function. Methods : Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin-4 (FE) or chloroquine (FCQ)...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28185715/effects-of-oral-antidiabetic-drugs-on-changes-in-the-liver-to-spleen-ratio-on-computed-tomography-and-inflammatory-biomarkers-in-patients-with-type-2-diabetes-and-nonalcoholic-fatty-liver-disease
#5
Koichi Yabiku, Akiko Mutoh, Kazufumi Miyagi, Nobuyuki Takasu
PURPOSE: Oral antidiabetic drugs (OADs) such as pioglitazone and metformin have beneficial effects in patients with nonalcoholic steatohepatitis. We prospectively assessed the effects of OADs on nonalcoholic fatty liver disease (NAFLD) in 886 men with type 2 diabetes mellitus and in a murine model of NAFLD. METHODS: Patients were randomized to receive pioglitazone, metformin, sitagliptin, or a non-OAD (control) for 6 months. All the patients received dietary and exercise guidance once a month during this study...
February 6, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28184166/canagliflozin-improves-risk-factors-of-metabolic-syndrome-in-patients-with-type-2-diabetes-mellitus-and-metabolic-syndrome
#6
Michael J Davies, Katherine W Merton, Ujjwala Vijapurkar, Dainius A Balis, Mehul Desai
OBJECTIVE: Metabolic syndrome refers to a collection of risk factors associated with the development of cardiovascular disease and type 2 diabetes mellitus (T2DM). Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves glycemic control and reduces body weight and blood pressure (BP) in a broad range of patients with T2DM. This post hoc analysis assessed the effects of canagliflozin on the components of metabolic syndrome in patients with T2DM and metabolic syndrome. METHODS: This analysis was based on data from 2 head-to-head studies of canagliflozin in patients with T2DM on background metformin versus glimepiride (study 1) and background metformin plus sulfonylurea versus sitagliptin 100 mg (study 2)...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28182722/hemoglobin-glycation-index-as-a-useful-predictor-of-therapeutic-responses-to-dipeptidyl-peptidase-4-inhibitors-in-patients-with-type-2-diabetes
#7
Yu-Wei Chen, Jun-Sing Wang, Wayne H-H Sheu, Shih-Yi Lin, I-Te Lee, Yuh-Min Song, Chia-Po Fu, Chia-Lin Lee
INTRODUCTION: A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. METHODS: This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level...
2017: PloS One
https://www.readbyqxmd.com/read/28179965/primary-care-based-investigation-of-the-effect-of-sitagliptin-on-blood-pressure-in-hypertensive-patients-with-type-2-diabetes
#8
Shouhei Yuasa, Kazuyoshi Sato, Takamoto Furuki, Kosuke Minamizawa, Hiroyuki Sakai, Yuichi Numata, Keiichi Chin, Jisho Kojima, Masaaki Miyakawa, Ikuro Matsuba
BACKGROUND: The influence of long-term sitagliptin therapy on office blood pressure (BP) and home BP has been unclear. METHODS: In a retrospective cohort study of 454 patients with type 2 diabetes, the following variables were analyzed before and at 3, 6, 9, and 12 months after initiation of sitagliptin therapy: office systolic blood pressure (SBP), office diastolic blood pressure (DBP), office pulse rate, morning home SBP, morning home DBP, morning home pulse rate, evening home SBP, evening home DBP, evening home pulse rate, hemoglobin A1c (HbA1c), plasma glucose, lipid profile, and renal function parameters...
March 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28179397/dipeptidyl-peptidase-4-induces-aortic-valve-calcification-by-inhibiting-insulin-like-growth-factor-1-signaling-in-valvular-interstitial-cells
#9
Bongkun Choi, Sahmin Lee, Sang-Min Kim, Eun-Jin Lee, Sun Ro Lee, Dae-Hee Kim, Jeong Yoon Jang, Sang-Wook Kang, Ki-Up Lee, Eun-Ju Chang, Jae-Kwan Song
Background -Calcification of the aortic valve leads to increased leaflet stiffness, and consequently to the development of calcific aortic valve disease (CAVD); however, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes CAVD progression. Methods -We obtained the aortic valve tissues from humans and murine models (wild type and eNOS(-/-) mice), and cultured the valvular interstitial cells (VICs) and valvular endothelial cells (VECs) from the cusps...
February 8, 2017: Circulation
https://www.readbyqxmd.com/read/28177527/effects-of-linagliptin-on-human-immortalized-podocytes-a-cellular-system-to-study-dipeptidyl-peptidase-4-inhibition
#10
Gianluca Miglio, Giovanna Vitarelli, Thomas Klein, Elisa Benetti
BACKGROUND AND PURPOSE: Dipeptidyl-peptidase (DPP)4 is expressed by resident renal cells, including glomerular cells. Dipeptidyl-peptidase 4 inhibitors (gliptins) exert albuminuria lowering effects, but the role of renal DPP4 as a pharmacological target has not been elucidated. To better understand the actions of gliptins, the effects of linagliptin on behaviour of immortalized human podocytes and mesangial cells have been evaluated. EXPERIMENTAL APPROACH: Expression of DPP4 was measured at both the mRNA and protein levels...
February 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28167482/beneficial-effects-of-sitagliptin-and-metformin-in-non-diabetic-hypertensive-and-dyslipidemic-patients
#11
Mazhar Hussain, Moazzam Ali Atif, Muhammad Bilal 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/28166651/dipeptidyl-peptidase-4-inhibitor-associated-risk-of-bleeding
#12
Md Motiur Rahman, Michael J Scalese, Richard A Hansen
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control, and sitagliptin has been associated with a reduction in cardiovascular events. In vivo data suggest reduced platelet activation, and aggregation may play a role, and therefore, increased bleeding risk is possible. OBJECTIVE: Comparatively assess bleeding risks associated with DPP-4 inhibitors against standard treatment. METHODS: Exploratory analyses of adverse event reports (AERs) from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2012 periods) were conducted...
February 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28157387/trigonelline-attenuates-hepatic-complications-and-molecular-alterations-in-high-fat-high-fructose-diet-induced-insulin-resistance-in-rats
#13
Nehal A Afifi, Amer Ramadan, Emad Y Erian, Dalia O Saleh, Ahmed A Sedik, Manal Badawi, Walid El Hotaby
The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines...
October 12, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28151518/-type-2-diabetes-treatment-and-cardiovascular-risk-what-can-we-learn-from-trials
#14
Agostino Consoli, Fabrizio Febo
Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28145158/impact-of-dpp-4-inhibition-on-acute-and-chronic-endothelial-function-in-humans-with-type-2-diabetes-on-background-metformin-therapy
#15
Michael E Widlansky, Venkata K Puppala, Tisha M Suboc, Mobin Malik, Amberly Branum, Kara Signorelli, Jingli Wang, Rong Ying, Michael J Tanner, Sudhi Tyagi
: Cell culture and animal work indicate that dipeptidyl peptidase-4 (DPP-4) inhibition may exert cardiovascular benefits through favorable effects on the vascular endothelium. Prior human studies evaluating DPP-4 inhibition have shown conflicting results that may in part be related to heterogeneity of background anti-diabetes therapies. No study has evaluated the acute response of the vasculature to DPP-4 inhibition in humans. We recruited 38 patients with type 2 diabetes on stable background metformin therapy for a randomized, double-blind, placebo-controlled crossover trial of DPP-4 inhibition with sitagliptin (100 mg/day)...
January 1, 2017: Vascular Medicine
https://www.readbyqxmd.com/read/28131656/integration-of-recent-evidence-into-management-of-patients-with-atherosclerotic-cardiovascular-disease-and-type-2-diabetes
#16
REVIEW
Eberhard Standl, Oliver Schnell, Darren K McGuire, Antonio Ceriello, Lars Rydén
Cardiovascular outcome trials of antihyperglycaemic drugs and non-statin LDL-cholesterol-lowering drugs in patients with type 2 diabetes who have, or who are at high risk of, atherosclerotic cardiovascular disease have provided new evidence that has substantially affected the management of cardiovascular risk in these patients. On the basis of proven cardiovascular and renal benefit, the antihyperglycaemic drugs empagliflozin, liraglutide, and semaglutide-the latter being under review for approval by the US Food and Drug Administration and the European Medicines Agency-should be preferentially used as second-line treatments in these patient populations, typically in addition to metformin...
January 25, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28121469/savor-timi-to-sustain-6-a-critical-comparison-of-cardiovascular-outcome-trials-of-antidiabetic-drugs
#17
Awadhesh Kumar Singh, Ritu Singh
Since the inception of mandatory cardiovascular (CV) safety outcome trial (CVOT) promulgated by US FDA in 2008, seven trials have so far been published with three different classes of antidiabetic drugs in type 2 diabetes mellitus (T2DM). This mini-review aims to critically analyse these CVOTs in terms of different outcomes achieved. Areas covered: An electronic search pertaining to the subject was conducted till September 2016. The three CVOT conducted with saxagliptin, alogliptin and sitagliptin respectively, found them to be CV-neutral...
February 6, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28119159/hindbrain-dpp-iv-inhibition-improves-glycemic-control-and-promotes-negative-energy-balance
#18
Elizabeth G Mietlicki-Baase, Lauren E McGrath, Kieran Koch-Laskowski, Joanna Krawczyk, Tram Pham, Rinzin Lhamo, David J Reiner, Matthew R Hayes
The beneficial glycemic and food intake-suppressive effects of glucagon-like peptide-1 (GLP-1) have made this neuroendocrine system a leading target for pharmacological approaches to the treatment of diabetes and obesity. One strategy to increase the activity of endogenous GLP-1 is to prevent the rapid degradation of the hormone by the enzyme dipeptidyl peptidase-IV (DPP-IV). However, despite the expression of both DPP-IV and GLP-1 in the brain, and the clear importance of central GLP-1 receptor (GLP-1R) signaling for glycemic and energy balance control, the metabolic effects of central inhibition of DPP-IV activity are unclear...
January 22, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28118607/middle-east-respiratory-syndrome-corona-virus-spike-glycoprotein-suppresses-macrophage-responses-via-dpp4-mediated-induction-of-irak-m-and-ppar%C3%AE
#19
Ahmed A Al-Qahtani, Konstantina Lyroni, Marina Aznaourova, Melpomeni Tseliou, Mashael R Al-Anazi, Mohammed N Al-Ahdal, Saad Alkahtani, George Sourvinos, Christos Tsatsanis
Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFα and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28105986/canagliflozin-dapagliflozin-and-empagliflozin-monotherapy-for-treating-type-2-diabetes-systematic-review-and-economic-evaluation
#20
Rhona Johnston, Olalekan Uthman, Ewen Cummins, Christine Clar, Pamela Royle, Jill Colquitt, Bee Kang Tan, Andrew Clegg, Saran Shantikumar, Rachel Court, J Paul O'Hare, David McGrane, Tim Holt, Norman Waugh
BACKGROUND: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors...
January 2017: Health Technology Assessment: HTA
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