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https://www.readbyqxmd.com/read/28934557/a-safety-evaluation-of-empagliflozin-plus-linagliptin-for-treating-type-2-diabetes
#1
Baptist Gallwitz
Dipeptidyl-peptidase-IV inhibitors (DPP-4i) and sodium-glucose-transporter-2 inhibitors (SGLT-2i) are oral antidiabetic drugs that improve glycemic parameters and possess a very low intrinsic hypoglycemia risk and favorable cardiovascular data. Areas covered: An overview on the clinical studies investigating the combination therapy with the DPP-4i linagliptin and the SGLT-2i empagliflozin is given. The clinical evidence for the efficacy and safety of free combinations as well as for their fixed dose combinations is presented...
September 21, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28933039/dose-dependent-effect-of-sitagliptin-on-carotid-atherosclerosis-in-patients-with-type-2-diabetes-mellitus-receiving-insulin-treatment-a-post-hoc-analysis
#2
Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce blood glucose in a dose-dependent manner, but the dose-dependent effect relationship between DPP-4 inhibitors and atherosclerosis has not been investigated. METHODS: Patients with type 2 diabetes mellitus (T2DM) treated with insulin were randomized to the sitagliptin (n = 137) or conventional treatment group (n = 137). In the sitagliptin group, each investigator was allowed to adjust the sitagliptin dose to avoid hypoglycemia...
September 20, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28931178/the-oral-dipeptidyl-peptidase-4-inhibitor-sitagliptin-increases-circulating-levels-of-stromal-derived-factor-1-alpha
#3
Athanasia K Papazafiropoulou, Nikolaos Papanas, Aikaterini Trikkalinou, Evaggelos Fousteris, Andreas Melidonis
Recent studies have demonstrated that stromal derived factor-1α (SDF-1α) is a substrate of dipeptidyl-peptidase-4 (DPP-4) inhibitors. It has also been shown that SDF-1α shares anti-apoptotic as well as nephroprotective properties and exerts a beneficial effect in the cardiovascular system. Therefore, the aim of this study was to estimate the effect of treatment with the DDP-4 inhibitor sitagliptin on SDF-1α levels in subjects with type 2 diabetes mellitus (T2D). Overall, 32 patients (16 males) with T2D, mean age (±SD) 67...
September 20, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28929327/possible-long-term-efficacy-of-sitagliptin-a-dipeptidyl-peptidase-4-inhibitor-for-slowly-progressive-type-1-diabetes-spiddm-in-the-stage-of-non-insulin-dependency-an-open-label-randomized-controlled-pilot-trial-span-s
#4
Takuya Awata, Akira Shimada, Taro Maruyama, Yoichi Oikawa, Nobuyuki Yasukawa, Susumu Kurihara, Yumi Miyashita, Masako Hatano, Yuichi Ikegami, Masafumi Matsuda, Masataka Niwa, Youichiro Kazama, Shoichiro Tanaka, Tetsuro Kobayashi
INTRODUCTION: We tested the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in preserving the β-cell function for long-term periods in patients with slowly progressive type 1 diabetes (SPIDDM) or latent autoimmune diabetes in adults (LADA). METHODS: In the present open-label, randomized, controlled trial, 14 non-insulin-requiring diabetic patients with glutamic acid decarboxylase autoantibodies (GADAb) were randomly assigned to receive either sitagliptin (S group) or pioglitazone (P group)...
September 19, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28928281/engrailed-acts-with-nejire-to-control-decapentaplegic-expression-in-the-drosophila-ovarian-stem-cell-niche
#5
Lichao Luo, Chia Keng Siah, Yu Cai
Homeostasis of adult tissues is maintained by a small number of stem cells, which are sustained by their niches. In the Drosophila female germline stem cell (GSC) niche, Decapentaplegic (Dpp) is the primary factor that promotes GSC self-renewal. However, the mechanism regulating dpp expression in the niche is largely unknown. Here, we identify a 2.0 kb fragment located in a 5' cis-regulatory region of the dpp locus containing enhancer activity that drives its expression in the niche. This region is distinct from a previously characterized 3' cis-regulatory enhancer responsible for dpp expression in imaginal discs...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28924042/alternative-cleavage-of-the-bone-morphogenetic-protein-bmp-gbb-produces-ligands-with-distinct-developmental-functions-and-receptor-preference
#6
Edward N Anderson, Kristi A Wharton
The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins have numerous developmental and physiological roles. They are made as proprotein dimers, then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer. Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms. Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, while NS site cleavage produces a larger Gbb38 ligand...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923291/use-of-prohibited-medication-a-potentially-overlooked-confounder-in-clinical-trials-omarigliptin-once-weekly-dpp-4-inhibitor-monotherapy-trial-in-18-to-45-year-olds
#7
Ira Gantz, Liubov Sokolova, Lokesh Jain, Carol Iredale, Edward A O'Neill, Ziwen Wei, Raymond Lam, Shailaja Suryawanshi, Keith D Kaufman, Samuel S Engel, Eseng Lai
PURPOSE: The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients. METHODS: Patients with T2DM who were ≥18 to <45 years of age and either drug-naive or not on an antihyperglycemic agent for ≥12 weeks with inadequate glycemic control were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 102) or placebo once weekly (n = 101) for 24 weeks...
September 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28923269/dpp-4-inhibition-protects-human-umbilical-vein-endothelial-cells-from-hypoxia-induced-vascular-barrier-impairment
#8
Naoko Hashimoto, Kento Ikuma, Yui Konno, Masanori Hirose, Hiroyuki Tadokoro, Hiroshi Hasegawa, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28921847/n-n-methylenebis-acrylamide-crosslinked-poly-acrylic-acid-particles-as-doxorubicin-carriers-a-comparison-between-release-behavior-of-physically-loaded-drug-and-conjugated-drug-via-acid-labile-hydrazone-linkage
#9
Seyedeh Mahnaz Modarresi-Saryazdi, Vahid Haddadi-Asl, Mehdi Salami-Kalajahi
N,N'-methylenebis(acrylamide) (MBA)-crosslinked poly(acrylic acid) (PAA) particles with low degree of crosslinking were synthesized using distillation precipitation polymerization (DPP). Size and size distribution of particles were obtained using DLS and FE-SEM and results showed that microspheres had a narrow size dispersity. (1) H NMR results indicated that amount of crosslinker in structure of particles is a little more than the molar percentage of feeded MBA due to greater activity ratio of MBA than AA...
September 18, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28915418/purification-identification-and-molecular-mechanism-of-two-dipeptidyl-peptidase-iv-dpp-iv-inhibitory-peptides-from-antarctic-krill-euphausia-superba-protein-hydrolysate
#10
Wei Ji, Chaohua Zhang, Hongwu Ji
Dipeptidyl peptidase IV (DPP-IV) played an important role in blood glucose regulation. Inhibition of DPP-IV may improve glycemic control in diabetics by preventing the rapid breakdown of incretin hormones and prolonging their physiological action. In this study, Antarctic krill (Euphausia superba) protein was hydrolyzed using animal proteolytic enzymes. The hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and reversed phase high-performance liquid chromatography (RP-HPLC)...
September 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#11
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28910556/probing-the-influence-of-sibling-proteins-on-collagen-i-fibrillogenesis-and-denaturation
#12
Chengyu Jiang, Kevin Zurick, Chunlin Qin, Matthew T Bernards
Bone tissue is comprised of collagen, non-collagenous proteins, and hydroxyapatite and the SIBLING (small integrin binding, N-linked glycoprotein) family of proteins is the primary group of non-collagenous proteins. By replicating the native interactions between collagen and the SIBLING family of proteins at the interface of an implant, it is believed that a bone scaffold will more easily integrate with the surrounding tissue. In this work bone sialoprotein (BSP), osteopontin (OPN), dentin sialoprotein (DSP), dentin phosphoprotein (DPP), C-terminal fragment of dentin matrix protein 1 (DMP1-C) and proteoglycan versions of DSP (DSP-PG) and DMP1 (DMP1-PG) were tested individually to determine their roles in collagen fibrillogenesis and the prevention of denaturation...
September 14, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28903385/dpp-4-enzyme-deficiency-protects-kidney-from-acute-ischemia-reperfusion-injury-role-for-remote-intermittent-bowel-ischemia-reperfusion-preconditioning
#13
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4(D)) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4(D)) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4(D), (3) KIR-F344 (4) KIR-DPP4(D), (5) DPP4(D)-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4(D) rats 72 h after acute KIR...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900135/hedgehog-signalling-is-required-for-cell-survival-in-drosophila-wing-pouch-cells
#14
Juan Lu, Dan Wang, Jie Shen
An appropriate balance between cell survival and cell death is essential for correct pattern formation in the animal tissues and organs. Previous studies have shown that the short-range signalling molecule Hedgehog (Hh) is required for cell proliferation and pattern formation in the Drosophila central wing discs. Signal transduction by one of the Hh targets, the morphogen Decapentaplegic (Dpp), is required for not only cell proliferation, but also cell survival in the pouch cells. However, Hh function in cell survival and cell death has not been revealed...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899989/dipeptidyl-peptidase-4-inhibitors-and-risk-of-heart-failure-in-patients-with-type-2-diabetes-mellitus-a-population-based-cohort-study
#15
Young-Gun Kim, Dukyong Yoon, Sooyoung Park, Seung Jin Han, Dae Jung Kim, Kwan-Woo Lee, Rae Woong Park, Hae Jin Kim
BACKGROUND: The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas. METHODS AND RESULTS: A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015...
September 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#16
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#17
REVIEW
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28893244/a-randomized-placebo-controlled-study-of-the-cardiovascular-safety-of-the-once-weekly-dpp-4-inhibitor-omarigliptin-in-patients-with-type-2-diabetes-mellitus
#18
Ira Gantz, Menghui Chen, Shailaja Suryawanshi, Catherine Ntabadde, Sukrut Shah, Edward A O'Neill, Samuel S Engel, Keith D Kaufman, Eseng Lai
BACKGROUND: Omarigliptin is a once-weekly (q.w.) oral DPP-4 inhibitor that is approved for the treatment of patients with type 2 diabetes mellitus (T2DM) in Japan. To support approval of omarigliptin in the United States, the clinical development program included a cardiovascular (CV) safety study. Subsequently, a business decision was made not to submit a marketing application for omarigliptin in the United States, and the CV safety study was terminated. Herein we report an analysis of data from that early-terminated study...
September 11, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28892258/sitagliptin-and-roux-en-y-gastric-bypass-modulate-insulin-secretion-via-regulation-of-intra-islet-pyy
#19
Claudia Guida, Laura J McCulloch, Mahdieh Godazgar, Sam D Stephen, Charlotte Baker, Davide Basco, Jiawen Dong, Duan Chen, Anne Clark, Reshma D Ramracheya
AIMS: The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme DPP-IV has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS)...
September 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28885325/combination-therapy-of-metformin-plus-dipeptidyl-peptidase-4-inhibitor-versus-metformin-plus-sulfonylurea-and-their-association-with-a-decreased-risk-of-cardiovascular-disease-in-type-2-diabetes-mellitus-patients
#20
Fei Wang, Yuan He, Rong Zhang, Qiang Zeng, Xiaolan Zhao
BACKGROUND: Clinical trials assessing the combination therapy of metformin plus dipeptidyl peptidase-4 inhibitors versus metformin plus Sulfonylureas on risk of cardiovascular disease, cardiovascular mortality and/or all-cause mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the combination therapy on the risk of cardiovascular disease, cardiovascular mortality and/or all-cause mortality in type 2 diabetes. METHODS: A systematic search of Medline/PubMed (from 2000 to September 2015), EMBASE (from 2000 to September 2015), and Web of Knowledge (from 2000 to September 2015) for research articles published in English was carried out to examine how combination therapy affects the risk of CVD mortality and/or all-cause mortality in T2DM patients...
September 2017: Medicine (Baltimore)
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