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Dpp 4 inhibitors

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https://www.readbyqxmd.com/read/29452961/dipeptidyl-peptidase-4-inhibitors-dpp-4i-combined-with-vitamin-d3-an-exploration-to-treat-new-onset-type-1-diabetes-mellitus-and-latent-autoimmune-diabetes-in-adults-in-the-future
#1
Marcelo Maia Pinheiro, Felipe Moura Maia Pinheiro, Maria Luisa Trabachin
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by destruction of pancreatic beta cells through cell injury caused primarily by cytotoxic T lymphocytes (CD8 + ). The pathophysiological basis of T1DM seems to be an imbalance between a reduced function of T regulatory lymphocytes and an increased inflammatory activity of Th17 lymphocytes caused by increased production of inflammatory cytokines, as IL-1β, IL-6, IL-17 and IFN-gamma due to environmental factors and genetic predisposition...
February 13, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29437648/cardiovascular-outcomes-associated-with-canagliflozin-versus-other-non-gliflozin-antidiabetic-drugs-population-based-cohort-study
#2
Elisabetta Patorno, Allison B Goldfine, Sebastian Schneeweiss, Brendan M Everett, Robert J Glynn, Jun Liu, Seoyoung C Kim
OBJECTIVE: To evaluate the cardiovascular safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, in direct comparisons with DPP-4 inhibitors (DPP-4i), GLP-1 receptor agonists (GLP-1RA), or sulfonylureas, as used in routine practice. DESIGN: Population based retrospective cohort study. SETTING: Nationwide sample of patients with type 2 diabetes from a large de-identified US commercial healthcare database (Optum Clinformatics Datamart)...
February 6, 2018: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29435776/effect-of-anagliptin-and-sitagliptin-on-low-density-lipoprotein-cholesterol-in-type-2-diabetic-patients-with-dyslipidemia-and-cardiovascular-risk-rationale-and-study-design-of-the-reason-trial
#3
Shinichiro Ueda, Michio Shimabukuro, Osamu Arasaki, Koichi Node, Takashi Nomiyama, Takeshi Morimoto
BACKGROUND: Reduction of low-density lipoprotein cholesterol (LDL-C) is important for patients with a high risk for atherosclerotic events, such as patients with diabetes and other risk factors. Anagliptin was reported to reduce LDL-C for 12 weeks in phase III trials regardless of the use of statins, but it is uncertain whether this effect is common to other dipeptidylpeptidase-4 (DPP-4) inhibitors. METHODS: A multicenter, randomized, open-label, parallel-group trial was conducted to confirm the superiority of anagliptin to sitagliptin in terms of the primary endpoint of reduction of LDL-C for 52 weeks in patients with type 2 diabetes and atherosclerotic vascular lesions, as well as the non-inferiority of anagliptin to sitagliptin in terms of change in hemoglobin A1c (HbA1c)...
February 12, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29430979/an-effective-treatment-approach-of-dpp-iv-inhibitor-encapsulated-polymeric-nano-particles-conjugated-with-anti-cd-4-mab-for-type-1-diabetes
#4
Mahesh Thondawada, Ashish Devidas Wadhwani, Dhanabal S Palanisamy, Hanumant Singh Rathore, Ramesh C Gupta, Pavan Kumar Chintamaneni, Malay K Samanta, Anil Dubala, Sameer Varma, Praveen T Krishnamurthy, Kuppusamy Gowthamarajan
Nanotechnology based bio-medical approaches and surface modification techniques made it easier for targeting specific site and improving the treatment efficacy. The present study reports on targeted polymeric nanoparticles conjugated with antibody as a site-specific carrier system for effective treatment of Type 1 diabetes. Sitagliptin (SP) loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) were prepared by nanoprecipitation cum solvent evaporation method and were characterized in terms of morphology, size, surface charge and entrapment efficiency...
February 12, 2018: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29412816/tissue-expression-of-dpp-iv-in-obesity-diabetes-and-modulatory-effects-on-peptide-regulation-of-insulin-secretion
#5
Aine M McKillop, Claire L Stevenson, Brian M Moran, Yasser H A Abdel-Wahab, Peter R Flatt
Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent an important class of glucose-lowering drug for type 2 diabetes. DPP-4 enzyme activity has been observed to be significantly altered in type 2 diabetes. Here, the role of DPP-4 was examined in a high fat fed (HFF) mouse model of insulin resistance. HFF mice had an increased bodyweight (p < .01), were hyperglycaemic (p < .01) and hyperinsulinaemic (p < .05). Compared to normal diet, HFF mice exhibited increased plasma DPP-4 activity (p < .01)...
February 2018: Peptides
https://www.readbyqxmd.com/read/29412814/peptide-degradation-and-the-role-of-dpp-4-inhibitors-in-the-treatment-of-type-2-diabetes
#6
Carolyn F Deacon
Dipeptidyl peptidase-4 (DPP-4) inhibitors are now a widely used, safe and efficacious class of antidiabetic drugs, which were developed prospectively using a rational drug design approach based on a thorough understanding of the endocrinology and degradation of glucagon-like peptide-1 (GLP-1). GLP-1 is an intestinal hormone with potent insulinotropic and glucagonostatic effects and can normalise blood glucose levels in patients with type 2 diabetes, but the native peptide is not therapeutically useful because of its inherent metabolic instability...
February 2018: Peptides
https://www.readbyqxmd.com/read/29411931/neuroprotective-mechanisms-of-glucagon-like-peptide-1-based-therapies-in-ischaemic-stroke-a-systematic-review-based-on-pre-clinical-studies
#7
Ida R Marlet, Joakim N E Ölmestig, Tina Vilsbøll, Jørgen Rungby, Christina Kruuse
Glucagon-like peptide-1 (GLP-1)-based therapies, GLP-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4Is) are widely used for the treatment of type 2 diabetes. Increasing evidence suggests that they may provide neuroprotection. The aim of this MiniReview was to systematically evaluate the proposed mechanism of action for GLP-1-based therapies in ischaemic brain damage in animals. We performed a literature search using Medline, Embase and The Cochrane Library. GLP-1-based therapies administered before, during or after experimental stroke in diabetic and non-diabetic animals were evaluated...
February 7, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29411416/decrease-in-eosinophils-infiltrating-into-the-skin-of-patients-with-dipeptidyl-peptidase-4-inhibitor-related-bullous-pemphigoid
#8
Chika Chijiwa, Shintaro Takeoka, Masahiro Kamata, Mihoko Tateishi, Saki Fukaya, Kotaro Hayashi, Atsuko Fukuyasu, Takamitsu Tanaka, Takeko Ishikawa, Takamitsu Ohnishi, Shinichi Watanabe, Yayoi Tada
Bullous pemphigoid (BP) is an acquired autoimmune blistering disease in which autoantibodies against epitopes in the basement membrane zone of the skin such as BP180 or BP230 are produced. Dipeptidyl peptidase (DPP)-4 inhibitors have become commonly used to treat diabetes. As DPP-4 inhibitors are more commonly prescribed for diabetes, BP related to DPP-4 inhibitors has been reported and has attracted attention. Therefore, we retrospectively investigated patients who were diagnosed with BP in order to examine characteristics of DPP-4 inhibitor-related BP (nine patients; median age, 85 years) in comparison with non-DPP-4 inhibitor-related BP (21; median age, 85 years)...
February 6, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29411291/post-liver-transplantation-diabetes-mellitus-a-review-of-relevance-and-approach-to-treatment
#9
REVIEW
Maria J Peláez-Jaramillo, Allison A Cárdenas-Mojica, Paula V Gaete, Carlos O Mendivil
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM...
February 6, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29409957/dpp-4-is-expressed-in-human-pancreatic-beta-cells-and-its-direct-inhibition-improves-beta-cell-function-and-survival-in-type-2-diabetes
#10
Marco Bugliani, Farooq Syed, Flavia M M Paula, Bilal A Omar, Mara Suleiman, Sandra Mossuto, Francesca Grano, Francesco Cardarelli, Ugo Boggi, Fabio Vistoli, Franco Filipponi, Paolo De Simone, Lorella Marselli, Vincenzo De Tata, Bo Ahren, Decio L Eizirik, Piero Marchetti
It has been reported that the incretin system, including regulated GLP-1 secretion and locally expressed DPP-4, is present in pancreatic islets. In this study we comprehensively evaluated the expression and role of DPP-4 in islet alpha and beta cells from non-diabetic (ND) and type 2 diabetic (T2D) individuals, including the effects of its inhibition on beta cell function and survival. Isolated islets were prepared from 25 ND and 18 T2D organ donors; studies were also performed with the human insulin-producing EndoC-βH1 cells...
January 31, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29403571/the-effects-of-a-sitagliptin-formulary-restriction-program-on-diabetes-medication-use
#11
Yuexin Tang, Xingyue Huang, Jinan Liu, R Ravi Shankar, Michael L Ganz, Swapnil Rajpathak
Background: Health plans have responded to the many treatment options for type 2 diabetes mellitus by implementing formulary restriction policies, including step therapy, to control costs. Little is known about the impact of step therapy programs on antidiabetes medication use. Objective: To assess the impact of a sitagliptin step therapy program on antidiabetes medication use among sitagliptin users. Methods: Using pharmacy claims from the Symphony Health Solutions' Integrated Dataverse, we compared the use of sitagliptin and other antidiabetes medications by patients enrolled in a health plan (Plan A) that implemented a sitagliptin step therapy program on July 1, 2013, with the use by patients who were contemporaneously enrolled in 2 comparison plans-Plans B and C-without step therapy programs...
December 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/29403151/new-insights-into-the-pharmacological-treatment-of-pediatric-patients-with-type-2-diabetes
#12
Tatsuhiko Urakami
The principal treatment for children and adolescents with type 2 diabetes is dietary and exercise management. However, the blood glucose levels of some patients receiving this treatment fail to improve; thus, pharmacological treatment is eventually required. The pathophysiology of type 2 diabetes in pediatric patients appears to be similar to that in adults; thus, the range of antidiabetic drugs used in adults is likely to be effective in pediatric patients as well. However, in the majority of countries, including Japan, only metformin, glimepiride, and insulin have been approved for use in pediatric patients...
2018: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
https://www.readbyqxmd.com/read/29402981/clinical-features-and-therapeutic-perspectives-on-hypertension-in-diabetics
#13
REVIEW
Shigehiro Katayama, Masako Hatano, Masashi Issiki
Over 50% of patients with diabetes mellitus, either type 1 or 2, ultimately develop hypertension as a complication. In diabetics, this further increases the incidence of cardiovascular disease (CVD) by 2- to 3-fold and accelerates the progression of diabetic nephropathy. Arteriosclerosis, a clinical feature of hypertension in diabetics, develops and advances from a young age. Therefore, in providing treatment, it is necessary to evaluate the degree of arteriosclerosis. Diabetic patients are encouraged to strictly control their blood glucose levels...
February 5, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/29394900/how-to-interpret-the-role-of-sdf-1%C3%AE-on-diabetic-complications-during-therapy-with-dpp-4-inhibitors
#14
EDITORIAL
Gian Paolo Fadini, Angelo Avogaro
No abstract text is available yet for this article.
February 2, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29391064/cost-effectiveness-analysis-of-metformin-dipeptidyl-peptidase-4-inhibitors-compared-to-metformin-sulfonylureas-for-treatment-of-type-2-diabetes
#15
Christina S Kwon, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio
BACKGROUND: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D...
February 1, 2018: BMC Health Services Research
https://www.readbyqxmd.com/read/29386477/evaluation-of-drug-efficacy-of-glp-1-receptor-agonists-and-dpp-4-inhibitors-based-on-target-molecular-binding-occupancy
#16
Risa Takayanagi, Takumi Uchida, Koji Kimura, Yasuhiko Yamada
Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, exenatide, lixisenatide) have recently been used as anti-diabetes drugs. We examined relationships of the binding occupancy of GLP-1 receptors (Φ) and their clinical efficacy after administration of GLP-1 receptor agonists. Next, by focusing on changes of GLP-1 concentration after administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, alogliptin, sitagliptin, linagliptin), we analyzed the relationship between Φ and clinical efficacy...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29386249/precision-medicine-in-type-2-diabetes-clinical-markers-of-insulin-resistance-are-associated-with-altered-short-and-long-term-glycemic-response-to-dpp-4-inhibitor-therapy
#17
John M Dennis, Beverley M Shields, Anita V Hill, Bridget A Knight, Timothy J McDonald, Lauren R Rodgers, Michael N Weedon, William E Henley, Naveed Sattar, Rury R Holman, Ewan R Pearson, Andrew T Hattersley, Angus G Jones
OBJECTIVE: A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy. RESEARCH DESIGN AND METHODS: We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study; n = 254), with replication for routinely available markers in U...
January 31, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29378454/possible-role-of-dpp4-inhibitors-to-promote-hippocampal-neurogenesis-in-alzheimer-s-disease
#18
Nehru Sai Suresh Chalichem, Pindiprolu S S Sai Kiran, Duraiswamy Basavan
As well-known to the scientific community that Alzheimer`s disease (AD) is an irreversible neurodegenerative disease that ends up with impairment of memory and cognition. Patient quality of life can be enhanced by targeting neurogenesis as a therapeutic paradigm. Preserving functional activity of SDF-1α and GLP-1 by DPPIV inhibition will enhance the homing of stem cells and modulates cell signaling pathways. The non-invasive approach presented in this article is a major advantage for managing AD, as regular/conventional stem-cell therapy necessarily relies on the application of regenerative stem cells exogenously...
January 30, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29376760/comparison-of-costs-and-outcomes-of-dapagliflozin-with-other-glucose-lowering-therapy-classes-added-to-metformin-using-a-short-term-cost-effectiveness-model-in-the-us-setting
#19
Abhiroop Chakravarty, Mohini Rastogi, Praveen Dhankhar, Kelly Bell
OBJECTIVE: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin. METHODS: A short-term decision-analytic model with a 1-year time horizon was developed from a payer's perspective in the United States (US) setting...
January 29, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29373269/surrogating-and-redirection-of-pyrazolo-1-5-a-pyrimidin-7-4h-one-core-a-novel-class-of-potent-and-selective-dpp-4-inhibitors
#20
Xinxian Deng, Jian Shen, Hui Zhu, Jia Xiao, Ran Sun, Fangzhou Xie, Celine Lam, Juntao Wang, Yixue Qiao, Mojdeh S Tavallaie, Yang Hu, Yi Du, Jianqi Li, Lei Fu, Faqin Jiang
The initial focus on characterizing novel pyrazolo[1,5-a]pyrimidin-7(4H)-one derivatives as DPP-4 inhibitors, led to a potent and selective inhibitor compound b2. This ligand exhibits potent in vitro DPP-4 inhibitory activity (IC50: 80 nM), while maintaining other key cellular parameters such as high selectivity, low cytotoxicity and good cell viability. Subsequent optimization of b2 based on docking analysis and structure-based drug design knowledge resulted in d1. Compound d1 has nearly 2-fold increase of inhibitory activity (IC50: 49 nM) and over 1000-fold selectivity against DPP-8 and DPP-9...
January 10, 2018: Bioorganic & Medicinal Chemistry
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